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Yi Que,1,* Yao Liang,2,* Jingjing Zhao,1 Ya Ding,1 Ruiqing Peng,1 Yuanxiang Guan,2 Xing Zhang1 1Department of Medical Melanoma and Sarcoma, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Gastric and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objective: Research efforts have investigated therapies targeting tyrosine kinase signaling pathways. We performed a pooled analysis to determine the frequency of severe adverse effects in patients with soft tissue sarcoma treated with pazopanib, sorafenib and sunitinib. Materials and methods: We performed a comprehensive search of PubMed, Web of Science, Ovid, the Cochrane Library and Embase databases from the drugs’ inception to May 2017 to identify clinical trials. All-grade and severe adverse events (AEs; grade≥3) were analyzed. Results: A total of 10 trials published between 2009 and 2016, including 843 patients, were eligible for analysis. We included 424 patients (three studies) who received pazopanib 800 mg daily, 353 patients (five studies) who received sorafenib 400 mg twice daily and 66 patients (two studies) who received sunitinib 37.5 mg daily. The incidence of AEs is different among the three VEGFR-tyrosine kinase inhibitors (TKIs). Pazopanib showed higher incidence of all-grade nausea, diarrhea and hypertension compared with sorafenib and sunitinib. However, patients in the sorafenib group experienced a significantly higher frequency of all-grade rash (26.1%), hand–foot syndrome (33.4%) and mucositis (38.5%). The difference was highly significant for sorafenib vs. pazopanib in the incidence of all-grade rash (odds ratio [OR] 1.649, 95% CI 1.086–2.505, P=0.023), hand–foot syndrome (OR 3.096, 95% CI 1.271–7.544, P=0.009) and mucositis (OR 4.562, 95% CI 2.132–9.609, P

Purpose: Ultrasound-guided percutaneous renal biopsy (PRB) has been considered as a golden standard for CKD diagnosis and is employed to identify potential therapeutic targets since 1950s. Post-biopsy hemorrhage is the most common complication, while severe bleeding complication might cause nephrectomy or death. Therefore, how to reduce the occurrence of complications while ensuring the success of PRB is always a clinical research topic., Methods: This study retrospectively collected and established a renal biopsy database of each patient who underwent ultrasound-guided PRB at a tertiary teaching hospital from September 2017 to December 2020 through the Health Information System. All the data were statistically processed by SPSS software., Results: A total of 1146 patients underwent PRB for various reasons. The overall rate of post-biopsy hemorrhage was 37.70% (432/1146). Of those bleedings, minor bleeding after PRB was found in 337 (29.41%), middle bleeding 84 (7.33%), major bleeding 11 (0.96%). Besides that, there were 96 patients (8.38%) reported their discomfort symptoms. There was no death. Females were at significantly increased risk of hemorrhagic complication than males (OR = 2.017, CI = 1.531-2.658). While the risk for hemorrhagic complication significantly decreased as BMI and platelet before renal biopsy increased (OR = 0.956, CI = 0.924-0.989; OR = 0.998, CI = 0.996-1.000). As the APTT time prolonged, the risk for hemorrhagic complication significantly increased (OR = 1.072, CI = 1.023-1.123). Those patients whose albumin were higher, also had higher risk for hemorrhagic complication than other patients (OR = 1.020, CI = 1.000-1.041). Specifically, postoperative urination within 4 h increased the risk for hemorrhagic complication (OR = 1.741, CI = 1.176-2.576)., Conclusion: Our analysis finds that the incidence of post-biopsy bleeding complication is 37.70%, and its risk is associated with female, lower BMI, lower platelet before renal biopsy, prolonged APTT, higher albumin, and postoperative urination within 4 h. The findings highlighted the importance of perioperative management for renal biopsy, including adequate risk assessment, tailored careful observation after PRB. And medical staff should pay more attention to fluid management after ultrasound-guided PRB., (© 2023. The Author(s).)

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The human microbiome exhibits a profound connection with the cancer development, progression, and therapeutic response, with particular emphasis on its components of the mycobiome, which are still in the early stages of research. In this review, we comprehensively summarize cancer-related symbiotic and pathogenic fungal genera. The intricate mechanisms through which fungi impact cancer as an integral member of both gut and tissue-resident microbiomes are further discussed. In addition, we shed light on the pivotal physiological roles of various nutrients, including cholesterol, carbohydrates, proteins and minerals, in facilitating the growth, reproduction, and invasive pathogenesis of the fungi. While our exploration of the interplay between nutrients and cancer, mediated by the mycobiome, is ongoing, the current findings have yet to yield conclusive results. Thus, delving into the relationship between nutrients and fungal pathogenesis in cancer development and progression would provide valuable insights into anticancer therapy and foster precision nutrition and individualized treatments that target fungi from bench to bedside., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

Alzheimer's disease (AD) is highly associated with self-aggregation of amyloid β (Aβ) proteins into fibrils. Inhibition of Aβ aggregation by polyphenols is one of the major therapeutic strategies for AD. Among them, four polyphenols (brazilin, resveratrol, hematoxylin, and rosmarinic acid) have been reported to be effective at inhibiting Aβ aggregation, but the inhibition mechanisms are still unclear. In this work, these four polyphenols were selected to explore their interactions with the Aβ17-42 pentamer by molecular dynamics simulation. All four polyphenols can bind to the pentamer tightly but prefer different binding sites. Conversion of the β-sheet to the random coil, fewer interchain hydrogen bonds, and weaker salt bridges were observed after binding. Interestingly, different Aβ17-42 pentamer destabilizing mechanisms for resveratrol and hematoxylin were found. Resveratrol inserts into the hydrophobic core of the pentamer by forming hydrogen bonds with Asp23 and Lys28, while hematoxylin prefers to bind beside chain A of the pentamer, which leads to β-sheet offset and dissociation of the β1 sheet of chain E. This work reveals the interactions between the Aβ17-42 pentamer and four polyphenols and discusses the relationship between inhibitor structures and their inhibition mechanisms, which also provides useful guidance for screening effective Aβ aggregation inhibitors and drug design against AD.

The chemical constituents of Chuanzhi Tongluo Capsules were analyzed and identified using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) to clarify the pharmacological substance basis. In addition, network pharmacology was employed to explore the mechanism of Chuanzhi Tongluo Capsules in the treatment of cerebral infarction. Gradient elution was performed using acetonitrile and 1% acetic acid in water as the mobile phase. Mass spectrometry was performed in positive and negative ion modes. Xcalibur 4.2 software was used for compound analysis, including accurate mass-to-charge ratio and MS/MS fragment information, combined with the comparison of reference standards and literature data. A total of 152 compounds were identified, including 32 organic acids, 35 flavonoids and their glycosides, 33 diterpenes, 13 phthalides, 12 triterpenes and triterpene saponins, 23 nitrogen-containing compounds, and 4 other compounds, and their fragmentation patterns were analyzed. SwissTargetPrediction, GeneCards, DAVID, and other databases were used to predict and analyze the core targets and mechanism of Chuanzhi Tongluo Capsules. Protein-protein interaction(PPI) network topology analysis identified 10 core targets, including TNF, VEGFA, EGFR, IL1B, and CTNNB1. KEGG enrichment analysis showed that Chuanzhi Tongluo Capsules mainly exerted their effects through the regulation of lipid and atherosclerosis, glycoproteins in cancer, MicroRNAs in cancer, fluid shear stress, and atherosclerosis-related pathways. Molecular docking was performed between the key constituents and core targets, and the results demonstrated a strong binding affinity between the key constituents of Chuanzhi Tongluo Capsules and the core targets. This study comprehensively elucidated the chemical constituents of Chuanzhi Tongluo Capsules and explored the core targets and mechanism in the treatment of cerebral infarction based on network pharmacology, providing a scientific reference for the study of the pharmacological substance basis and formulation quality standards of Chuanzhi Tongluo Capsules.

Alzheimer's disease (AD) is one of the most serious neurodegenerative diseases with no effective treatment options available. The formation of insoluble amyloid fibrils of the hyperphosphorylated tau protein is intimately associated with AD, hence the tau protein has been a key target for AD drug development. In this work, hematoxylin was discovered as a dual functional compound, that is, acting in the inhibition of repeat domain of tau (tau-RD) protein fibrillogenesis and remodeling of pre-formed tau-RD fibrils in vitro. Meanwhile, hematoxylin was able to reduce the accumulation of tau-RD aggregates in Saccharomyces cerevisiae. Experimental and computational studies indicated that hematoxylin directly interacts with tau-RD protein through hydrophobic forces, hydrogen bonds, π-cation interactions, and π-π stackings. In addition, cellular viability assays showed that hematoxylin greatly reduced cytotoxicity induced by tau-RD aggregates. In summary, hematoxylin might be a promising candidate for further development as a potential therapeutic drug for AD patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: We sought to evaluate the impact of the time interval from surgical resection to local recurrence (TTLR) on clinical outcomes in head and neck soft tissue sarcoma (HNSTS)., Methods: A total of 401 patients who underwent R0 resection for primary HNSTS were included in this study. Patients with local recurrence as the first event after their initial resection were divided into early local recurrence (ELR) or late local recurrence (LLR) groups according to TTLR. Multiple survival analyses were performed to identify the independent prognostic predictors of overall survival (OS) and survival after local recurrence (SAR)., Results: Two hundred and nine of the 401 patients (52.1%) developed local recurrence during a median follow-up period of 134.6 months. Patients in the ELR group had a shorter median OS time (35.0 vs. 120.6, p < 0.001) and lower 5-year OS rate (47.7% vs. 80.9%, p < 0.001) than those in the LLR group. Moreover, the ELR group exhibited worse SAR (p = 0.001) than the LLR group, and multivariate analyses demonstrated TTLR as an independent prognostic factor for SAR (p = 0.048) and OS (p = 0.004). Additionally, re-resection significantly prolonged SAR than other salvage interventions or no treatment (p < 0.001)., Conclusion: In patients with HNSTS, ELR after R0 resection presents adverse effects on OS and SAR than those with LLR, and TTLR could serve as a promising predictor for survival. Salvage therapies, especially the re-resection could improve SAR and should be recommended when there are surgical indications after recurrence., Level of Evidence: 3 Laryngoscope, 133:2174-2182, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: This study aimed to investigate the effect of cognitive load on anticipatory postural adjustment (APA) latency in patients with non-specific chronic low back pain (NCLBP) and its relationship with pain-related functional changes., Methods: A cross-sectional study was conducted from December 15, 2022 to January 25, 2023. Participants were divided into a healthy control group (n = 29) and an NCLBP group (n = 29). Each group was assigned a single task of rapid arm raising and a dual task of rapid arm raising combined with a cognitive load. The cognitive load task was conducted using visual conflict. The APA latency for bilateral trunk muscles was observed using electromyography. The duration of electromyography recording in each task cycle was 28 s. Pain related-functional changes were evaluated using Roland-Morris Disability Questionnaire (RMDQ) before all tasks., Results: The APA latency for the right multifidus was significantly delayed in the NCLBP group [25.38, 95% confidence interval (CI) 13.41-37.35] than in the healthy control group (- 5.80, 95% CI - 19.28 to 7.68) during dual task (p = 0.0416). The APA latency for the right multifidus (25.38, 95% CI 13.41-37.35) and transverse abdominis/internal oblique (29.15, 95% CI 18.81-39.50) were significantly delayed compared with on the left side in the NCLBP group during dual task (- 3.03, 95% CI - 15.18-9.13, p = 0.0220; 3.69, 95% CI - 6.81 to 14.18, p = 0.0363). The latency delay of the right and left multifidus APA in the NCLBP group under the dual-task was positively correlated with RMDQ scores (r = 0.5560, p = 0.0017; r = 0.4010, p = 0.0311)., Conclusions: Cognitive load could induce APA delay in the right trunk muscles and co-activation pattern changes in bilateral trunk muscle APA in patients with NCLBP. The APA onset delay in multifidus is positively related to pain-related daily dysfunction. Trial Registration ChiCTR2300068580 (retrospectively registered in February 23, 2023)., (© 2023. The Author(s).)

Colon-targeted oral drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC), which is a disease with high relapse and remission rates associated with immune system inflammation and dysregulation localized within the lining of the large bowel. However, the success of current available approaches used for colon-targeted therapy is limited. Budesonide (BUD) is a corticosteroid drug, and its rectal and oral formulations are used to treat UC, but the inconvenience of rectal administration and the systemic toxicity of oral administration restrict its long-term use. In this study, we designed and prepared colon-targeted solid lipid nanoparticles (SLNs) encapsulating BUD to treat UC by oral administration. A negatively charged surfactant (NaCS-C12) was synthesized to anchor cellulase-responsive layers consisting of polyelectrolyte complexes (PECs) formed by negatively charged NaCS and cationic chitosan onto the SLNs. The release rate and colon-specific release behavior of BUD could be easily modified by regulating the number of coated layers. We found that the two-layer BUD-loaded SLNs (SLN-BUD-2L) with a nanoscale particle size and negative zeta potential showed the designed colon-specific drug release profile in response to localized high cellulase activity. In addition, SLN-BUD-2L exhibited excellent anti-inflammatory activity in a dextran sulfate sodium (DSS)-induced colitis mouse model, suggesting its potential anti-UC applications., (© 2023. The Author(s).)

Background: The purpose of this scoping review was to organize and describe the literature on the application of clown care to the elderly population in nursing homes, including intervention time, intervention methods and intervention effects, so as to provide reference ideas for other scholars to explore clown care programs suitable for the elderly population in nursing homes., Methods: Employing Arksey and O'Malley's methodology, we searched for PubMed, Web of Science, Embase, Cochrane, CNKI, WanFang, VIP, and CBM systematically and thoroughly, and the search period was from the establishment of each database to December 12, 2022. Two researchers with evidence-based learning experience independently conducted literature retrieval, information extraction, and cross-checking in strict accordance with the inclusion and exclusion criteria. The review process is reported according to PRISMA., Results: 148 literature were initially obtained after searching, of which 18 were finally included. Among them, 17 were in English and 1 was in Chinese. There are 16 quantitative studies and 2 qualitative studies published from 2010 to 2022. It is found that the current clown care intervention program has not established a unified intervention standard and effective evaluation program., Conclusions: The results of this scoping review conclude that clown care played a significant role in the nursing home. At first, it can reduce negative emotions, cognitive impairments and physical pain among older adults. In addition, it can improve their quality of life, life satisfaction, etc. It is suggested to learn from the advanced experience of clown care in foreign countries and carry out more clown care among the elderly population in nursing homes in China., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

MiR-1283 has been identified as a tumor suppressor in some malignancies. Whereas, the role of miR-1283 in HER2-positive (HER2+) breast cancer, particularly its role in regulating cell proliferation, one of the most significant features of tumor progression, is unclear. The related microRNA screened by the breast cancer sample GSE131599 dataset were detected in HER2+ breast cancer tissues and cell lines. Then, the obtained miR-1283 was overexpressed in SKBR3 and BT-474 cells followed by relevant functional assays concerning cell proliferation and apoptosis. The xenograft mouse model was induced and the effect of miR-1283 on tumor growth and cell proliferation was examined. The target of miR-1283 and the transcription factor regulating miR-1283 were predicted and identified. Finally, the influence of transcription factor KLF14 on cell proliferation and apoptosis was investigated. An integrated analysis confirmed that miR-1283 expression was significantly decreased in HER2+ breast cancer tissues. Also, by q-RT-PCR detection, miR-1283 expression was markedly reduced in HER2+ breast cancer tissues and cell lines. The miR-1283 overexpression prevented the proliferation and enhanced apoptosis of HER2+ breast cancer cells, as well as inhibited tumor growth. Mechanistically, miR-1283 inhibited TFAP2C expression by targeting the 3'-untranslated regions of TFAP2C messenger RNA, and the KLF14 enhanced miR-1283 level via binding to its promoter. The result subsequently confirmed the KLF14/miR-1283 signaling suppressed cell proliferation in HER2+ breast cancer. Our results suggested that the KLF14/miR-1283/TFAP2C axis inhibited HER2+ breast cancer progression, which might provide novel insight into mechanical exploration for this disease., (© 2023 Wiley Periodicals LLC.)

Electrocardiogram (ECG) is a low-cost, simple, fast, and non-invasive test. It can reflect the heart's electrical activity and provide valuable diagnostic clues about the health of the entire body. Therefore, ECG has been widely used in various biomedical applications such as arrhythmia detection, disease-specific detection, mortality prediction, and biometric recognition. In recent years, ECG-related studies have been carried out using a variety of publicly available datasets, with many differences in the datasets used, data preprocessing methods, targeted challenges, and modeling and analysis techniques. Here we systematically summarize and analyze the ECG-based automatic analysis methods and applications. Specifically, we first reviewed 22 commonly used ECG public datasets and provided an overview of data preprocessing processes. Then we described some of the most widely used applications of ECG signals and analyzed the advanced methods involved in these applications. Finally, we elucidated some of the challenges in ECG analysis and provided suggestions for further research.

Objective: Obesity is characterized by excess fat accumulation and closely associated with insulin resistance and type 2 diabetes. We aimed at exploring the potential effect and mechanism of escin for the treatment of obesity using network pharmacology, and to verify the effect of escin on obese mice., Materials and Methods: Escin targets were predicted by DrugBank and SwissTarget database. Potential targets for the treatment of obesity were identified based on the DisGeNET database. Comparative analysis was used to investigate the overlapping genes between escin targets and obesity treatment-related targets. Using STRING database and Cytoscape to analyze interactions among overlapping genes, hub genes were identified. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted in DAVID. High-fat diet (HFD) -induced obese mice were used to observe the anti-obesity effects of escin. The body weight, relevant biochemical markers and HE staining of fat and liver tissues were determined after escin was administered for 18 weeks., Results: We screened 53 overlapping genes for escin and obesity. The mechanism of intervention of escin in treating obesity may involve 10 hub targets (STAT3, MTOR, NR3C1, IKBKB, PTGS2, MMP9, PRKCA, PRKCD, AR, CYP3A4). The screening and enrichment analysis revealed that the treatment of obesity using escin primarily involved 10 GO enriched terms and 13 related pathways. In vivo, escin can reduce the body weight of obese mice induced by HFD and improve lipid metabolism through lowering triglycerides (TG), total cholesterol (TC), and density lipoprotein (LDL) levels and increasing high density lipoprotein (HDL) levels and decreasing leptin level and increasing adiponectin (ADPN) level. Escin can regulate glucose metabolism caused by obesity through decreasing fasting glucose, postprandial blood glucose and regulating the level of insulin. These obese mice induced by HFD displayed the increased insulin resistance that was associated with the increased inflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Escin may antagonize the increase of MCP-1 and partially antagonize the low-grade inflammation caused by obesity. From the morphological changes of fat and liver tissues stained by HE stain, escin could decrease the size of adipocytes and improve liver necrosis and fatty degeneration in obese mice fed by HFD., Conclusions: The network pharmacology of escin in treating obesity may involve 10 hub targets (STAT3, MTOR, NR3C1, IKBKB, PTGS2, MMP9, PRKCA, PRKCD, AR, CYP3A4), 10 GO enriched terms and 13 related pathways. In vivo, escin can be potentially used to prevent or treat obesity through reducing the weight, improving glucose and lipid metabolism, partially antagonizing the low-grade inflammation, and improved insulin resistance.

Diabetic retinopathy (DR) is one of the common systemic complications of diabetes. Epithelial-mesenchymal transition (EMT) is required for DR progression. Previous studies have explored that circular RNAs (circRNAs) are crucial for DR development. Herein, we focused on the biological functions of circSCMH1 in DR. RT-qPCR determined the expression of circSCMH1, miR-200a-3p and ZEB1. EMT-related proteins were measured by Western blot. Gene combinations were validated by RIP and dual luciferase reporter assays. CCK-8, EdU, TUNEL staining and Transwell analysis were used to assess the cellular function. FISH analysis assessed the localization of circSCMH1 and miR-200a-3p. HE staining was used to detect retinal structures in a mouse DR model. High-glucose (HG) significantly increased circSCMH1 expression in ARPE-19 cells. Additionally, circSCMH1 silencing repressed proliferation, migration, and EMT in HG cells. Mechanistically, circSCMH1 positively regulated ZEB1 expression via targeting miR-200a-3p. Furthermore, circSCMH1 was observed to induce HG cell growth and EMT by regulating the miR-200a-3p/ZEB1 axis. Finally, we verified that downregulation of circSCMH1 or ZEB1 alleviated EMT in the retina of diabetic mice. These findings have implications for new therapeutic targets for DR., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study aims to explore the effect of Jingfang Mixture on the protein expression of urticaria in mice and explain the mechanism of Jingfang Mixture in the treatment of urticaria. Twenty-seven male Kunming mice were randomly divided into a normal group, a model group and a Jingfang Mixture group according to body weight. Except for the normal group, mice in the model group and the Jingfang Mixture group were injected with the mixture of ovalbumin and Al(OH)&#95;3 gel for the first immunization, and the second immunization was performed on the 10 th day to induce the urticaria model. Mice in the Jingfang Mixture group started to be administered on the 6 th day after the initial immunization, and was administered continuously for 21 days. The normal group and the model group were replaced with the same amount of purified water. Twenty-four hours after the last administration, an appropriate amount of skin was taken, and label-free quantitative proteomics technology was used to detect the differences in protein expression in skin tissue. The signaling pathways involved in the differential proteins was further analyzed. The results of proteomics indicated that seventy-six proteins were involved in the intervention of Jingfang Mixture on mice with urticaria, and the differential proteins were mainly enriched in biological process(BP), molecular function(MF), and cellular component(CC). Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that the signaling pathways regulated by Jingfang Mixture mainly involved carbon metabolism, metabolic pathways, glucagon signaling pathway, glycolysis/gluconeogenesis, pentose phosphate pathway, hypoxia inducible factor-1(HIF-1) signaling pathway, purine metabolism, adherens junction, calcium signaling pathway, leukocyte transendothelial migration, and inflammatory mediator regulation of transient receptor potential(TRP) channels, which were involved in skin tissue energy metabolism and immune regulation. The findings of this study showed that the protective effect of Jingfang Mixture on mice with urticaria was closely related to the regulation of immune disorders, and the regulatory effect on immune system may be achieved through the regulation of energy metabolism by Jingfang Mixture.

Objective: To explore the promotion effect of laparoscopic standardized surgery for gastric cancer observational in some regional medical centers in Shanghai. Methods: A retrospective cohort study was carried out. Eleven regional medical centers in Shanghai received the promotion program of laparoscopic standardized surgery for gastric cancer, which was led by Ruijin Hospital, Shanghai Jiaotong University School of Medicine (Shanghai Minimally Invasive Surgery Center) from January to December 2020. Clinicopathological data of gastric cancer patients treated at these 11 regional medical centers before and after the promotion program were collected. Inclusion criteria were as follows: patients undergoing laparoscopic distal gastrectomy or total gastrectomy; gastric cancer confirmed by pathology; without distant metastasis or peritoneal metastasis. Patients who did not undergo laparoscopic D2 radical resection, or received neoadjuvant chemotherapy before surgery, or without complete clinical data were excluded. Patients undergoing laparoscopic surgery from January to December 2019 were included in the pre-promotion group (46 cases). Patients undergoing laparoscopic surgery from January to December 2021 were included in the post-promotion group (102 cases). In addition, patients undergoing laparoscopic surgery at Ruijin Hospital from January 2021 to December were included in the control group (138 cases). The baseline data, perioperative measurements postoperative complications, and pathological results of the three groups were analyzed and compared. Results: There were no significant differences in baseline characteristics among the three groups (all P >0.05). Compared with the pre-promotion group, the operation time in post-promotion group was significantly shorter [(207.3±36.0) minutes vs. (254.2±47.1) minutes, t =7.038, P <0.001], and the number of harvested lymph node was significantly more (24.4±12.2 vs. 18.9±5.5, t =2.900, P =0.004). However, there were no significant differences in the extent of resection, time to fluid intake, and postoperative hospital stay between the two groups (all P >0.05). Compared with the control group, the operation time [(207.3±36.0) minutes vs (172.6±26.0) minutes, t =8.281, P <0.001], time to fluid intake [(6.3±3.2) days than (5.5±3.0) days, t =2.029, P =0.044], and the postoperative hospital stay [(14.3±5.6) days vs. (10.1±4.8) days, t =6.036, P <0.001] in the post- promotion group were still longer. Total gastrectomy was less common in the post-promotion group compared with the control group [18 cases (17.6%) vs. 41 cases (29.7%), χ 2 =7.380, P =0.007]. However, there was no significant difference in the number of harvested lymph node between the two groups ( P >0.05). The morbidity of postoperative complication in the post-promotion group (9.8%, 10/102) was significantly lower than that in the pre-promotion group (23.9%, 11/46) (χ 2 =5.183, P =0.023), while above morbidity was not significantly different between the post-promotion group and the control group [9.8% vs. 6.5% (9/138), χ 2 =0.867, P =0.352]. Conclusion: After the promotion of laparoscopic standardized surgery for gastric cancer in regional medical centers, the standardization degree of surgery has been improved, and the morbidity of postoperative complication decreases. Laparoscopic standardized surgery for gastric cancer can be promoted to more regional medical centers.

Rice-wheat rotation is one of the most intensive agricultural planting modes in China and is pivotal to develop optimized straw-returning management in situ to improve soil fertility and productivity in agricultural ecosystems. Previous studies have mainly focused on the effects of straw return with a single application of organic fertilizers. The integrated management of different fertilizers in improving the management of straw return in situ is not well known. In this study, a field experiment was conducted from 2017 to 2019 to explore the effects of a combined system of modified organic substrate (MOS) and straw-degrading compound microbial agent (CMA) on soil physiochemical properties, labile organic carbon, microbial activities, and soil microbial community composition under the background of direct crop straw return and chemical fertilizer utilization. Four treatments were designed: (1) control check; (2) CMA; (3) MOS; and (4) MOS + CMA. The results showed that the MOS + CMA treatment had the combined advantages of soil organic matter (SOM) accumulation, soil nutrient increase and soil microbial community alteration, which may be more suitable for improving the quality and fertility of sandy loam soil. This study provides novel insights for further understanding the effects of organic substrates and composite microbial agents on SOM changes and microbial community composition and function in the field, which has important implications for sustainable crop production and agricultural development., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Circular RNAs (circRNAs) are pivotal regulators of various human cancers and circ-ERBB2 is abnormally expressed in breast cancer cells. However, the role and mechanism of circ-ERBB2 in HER2-positive breast cancer are still unknown., Methods: The circ-ERBB2 expressions in the tumor tissues of HER2-positive breast cancer patients were tested using quantitative real-time PCR. The circ-ERBB2 function was investigated by cell counting kit 8 assay, Transwell, flow cytometry and Western blot. Mechanistically, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter gene assays were conducted to confirm the interaction between circ-ERBB2 and miR-136-5p or miR-198 in HER2-positive breast cancer cells., Results: Circ-ERBB2 was elevated in the tumor tissues of HER2-positive breast cancer patients. Functionally, the interference with circ-ERBB2 repressed HER2-positive breast cancer cell proliferation, migration, invasion and accelerated cell apoptosis. Furthermore, the mechanistic analysis corroborated that circ-ERBB2 acted as a competing endogenous RNA for miR-136-5p or miR-198 to relieve the repressive influence of miR-136-5p or miR-198 on its target transcription factor activator protein 2C (TFAP2C). Meanwhile, in vivo assays further corroborated the oncogenic function of circ-ERBB2 in HER2-positive breast cancer., Conclusions: Circ-ERBB2 accelerated HER2-positive breast cancer progression through the circ-ERBB2/miR-136-5p/TFAP2C axis or the circ-ERBB2/miR-198/TFAP2C axis., (© 2021. The Author(s).)

Assessment of the status property(boiling time) is a challenge for the quality control of extraction process in pharmaceutical enterprises. In this study, the pilot extraction process of Phellodendron chinense was used as the research carrier to develop an online near-infrared(NIR) quality control method based on the status property(boiling time). First, the NIR spectra of P. chinense were collected during the two pilot-scale extraction processes, and the status property(boiling time) was assessed by observing the state of bubbles in the extraction tank using a transparent window during the extraction process, which was then used as a reference standard. Based on the moving block standard deviation(MBSD) algorithm, the assessment model using online NIR spectra for boiling time during extraction process was established. In addition, the model was optimized as follows: standard normal variable(SNV) for spectral pretreatment, modeling band of 800-2 200 nm, and window size of 4. The results showed that, with 0.002 0 as the MBSD model threshold, the boiling time can be accurately assessed using online NIR spectra during extraction process. Furthermore, the principal component analysis-moving block standard deviation(PCA-MBSD) model was developed by our group to reduce the influence of online NIR spectral noise and background signal on the model, and the number of principal components was optimized into 2 in the PCA-MBSD model. The results showed that, with 0.000 075 as the PCA-MBSD model threshold, the boiling time can be accurately assessed using online NIR spectra during extraction process, with improved reliability. This study can provide a assessment method for boiling time during extraction process using online NIR spectra, which can replace the empirical judgment in manual observation, and realize the digitalization of the extraction process for big brand traditional Chinese medicine.

The physical properties of ginkgo leaves extract(GLE) are the critical quality attributes for the control of the manufacturing process of ginkgo leaves preparations. In this study, 53 batches of GLE with different sources from the real world were used as the objects to carry out the research from 3 levels. First, based on micromeritics evaluation method, a total of 29 physical attribute quality parameters in five dimensions were comprehensively characterized, with a total of 1 537 data points. Further, with use of physical fingerprinting technology combined with similarity evaluation, the powder physical properties of 53 batches of GLE showed obvious differences from an overall perspective, and the similarity of the physical fingerprints was 0.876 to 1.000. Secondly, hierarchical clustering analysis(HCA) and principal component analysis(PCA) models were constructed to realize the reliable identification and differentiation of real-world materials produced by GLE from different sources. Multivariate statistical process control(MSPC) model was used to create GLE material Hotelling T~2 and squared prediction error(SPE) control charts. It was found that the SPE score of B&#95;(21) powder exceeded the 99% confidence control limit by 22.495 9, and the SPE scores of A&#95;1 and C&#95;(10) powder exceeded the 95% confidence control limit by 16.099 2, realizing the determination of abnormal samples in the materials of GLE from the production in real world. Finally, the physical quality control method of GLE in the production process of ginkgo leaves preparations was established in this study, providing a reference for the quality control methods of ginkgo leaves preparations in their manufacturing process.

Three compounds, including scolosprine C(1), uracil(2) and hypoxanthine(3), were isolated and purified from the ethyl acetate fraction of centipede by silica gel normal-phase column chromatography, reversed-phase medium pressure preparation chromatography, and high-pressure semi-preparative HPLC. The structure was elucidated through a combination of spectroscopic analyses [such as nuclear magnetic resonance(NMR) and mass spectrometry(MS)] and literature review. Among them, compound 1 was a new quinoline alkaloid. In previous reports, we have described the isolation and structure elucidation of one new and two known quinoline alkaloids. In this paper, we would report the isolation and structure elucidation of scolosprine C in detail.

BACKGROUND Myasthenia gravis (MG) is an autoimmune neurological disorder of neuromuscular junctions. In this study we established experimental autoimmune myasthenia gravis (EAMG) rat models to investigate the effects of AEB-071 (AEB), which is a specific inhibitor of protein kinase C that prevents T lymphocyte activation. MATERIAL AND METHODS We utilized animals divided into 4 groups: (1) control rats, (2) EAMG, (3) AEB-071+EAMG, and (4) AZP+EAMG. Drug treatment was continued for 10 days. Ten weeks after immunization we measured body weights, assessed mortality rates, and used Lennon scores to evaluate EAMG grades. We also assessed the proportions of Treg, Th1, Th2, Th17, and lymphocytes using flow cytometry. RESULTS In the absence of drug treatment, we found a significant decline in body weights in the EAMG group in comparison to control rats, and EAMG group rats also had higher Lennon scores (P<0.05). Interestingly, we found that AEB-071 restored the body weight of EAMG rats and the decreased mortality rate compared to AZP treatment. Although a decrease in the number of Treg cells was observed, the proportion of Th lymphocytes was significantly increased in the EAMG group, and AEB-071 treatment decreased the proportion of Th lymphocytes. CONCLUSIONS We concluded that AEB-071 treatment imparts beneficial effects in EAMG rat models by reducing mortality rate and restoring Th lymphocyte balance, and thus may be an attractive candidate for use in MG treatment.

Natural polymers like polysaccharides, polypeptides and their derivatives are broadly applied in drug delivery due to excellent biocompatibility and biodegradability. In this study, the dissolving tablets, formed with carboxymethylcellulose/poly-l-lysine/tripolyphosphate (CMC/PLL/TPP) complex, were prepared using metformin hydrochloride (MetHCl) as model drug. Confocal laser scanning microscopy observation manifested that FITC-labeled PLL interacted with CMC and formed a uniform interior microstructure. Scanning electron microscope images showed the drug-loaded tablets had well-formed shapes with smooth surfaces. MetHCl embedded interior the microstructures of the tablets and represented in a crystal form. Thermo-gravimetric analysis and differential scanning calorimetry indicated that the drug-loaded tablets had stable thermal properties with less moisture content (3.52%). Fourier transform infrared spectrometer confirmed that the CMC/PLL/TPP complex was fabricated via the electrostatic interactions between -NH 3 + , -COO - and -[P 2 O 5 4 -] - groups. The drug-loaded tablets had a high drug loading efficiency of 85.76% and drug encapsulation efficiency of 81.47%, and a shorter wetting time of 2.16 min in SSF (pH 6.8) and lower swelling ratio of 233.34%. The drug loaded in the samples could be released completely within 10 min in simulated saliva fluid (SSF pH 6.8), indicating a rapid drug release and dissolving profile in the environment, which could be developed for dissolving tablets., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

According to the classification of traditional Chinese medicine syndromes of coronavirus disease 2019 by the national competent authority, this study determined that human coronavirus 229 E(HCoV-229 E) was infected in a mouse model of cold and dampness syndrome, so as to build the human coronavirus pneumonia with pestilence attacking lung syndrome model. The model can simulate the traditional Chinese medicine treatment of common disease syndromes in Coronavirus Disease 2019 Diagnosis and Treatment Program(the sixth edition for trial). Specific steps were as follows. ABALB/c mouse model of cold and dampness syndrome was established, based on which, HCoV-229 E virus was infected; then the experiment was divided into normal control group, infection control group, cold-dampness control group, cold-dampness infection group(the model group), high-dose Chaiyin Particles group(8.8 g·kg~(-1)·d~(-1)), and low-dose Chaiyin Particles group(4.4 g·kg~(-1)·d~(-1)). On the day of infection, Chaiyin Particles was given for three consecutive days. Lung tissues were collected the day after the last dose, and the lung index and inhibition rate were calculated. The nucleic acid of lung tissue was extracted, and the HCoV-229 E virus load was detected by Real-time fluorescent quantitative RT-PCR. Blood leukocytes were separated, and the percentage of T and B lymphocytes was detected by flow cytometry. Lung tissue protein was extracted, and IL-6, IL-10, TNF-α and IFN-γ contents were detected by ELISA. High and low-dose Chaiyin Particles significantly reduced the lung index(P&lt;0.01) of mice of human coronavirus pneumonia with pestilence attacking the lung syndrome, and the inhibition rates were 61.02% and 55.45%, respectively. Compared with the model control group, high and low-dose Chaiyin Particles significantly increased cross blood CD4~+ T lymphocytes, CD8~+T lymphocytes and total B lymphocyte percentage(P&lt;0.05, P&lt;0.01), and reduced IL-10, TNF-α and IFN-γ levels in lungs(P&lt;0.01). In vitro results showed that TC&#95;(50), TC&#95;0, IC&#95;(50) and TI of Chaiyin Particles were 4.46 mg·mL~(-1), 3.13 mg·mL~(-1), 1.12 mg·mL~(-1) and 4. The control group of in vitro culture cells had no HCoV-229 E virus nucleic acid expression. The expression of HCoV-229 E virus nucleic acid in the virus control group was 1.48×10~7 copies/mL, and Chaiyin Particles significantly reduced HCoV-229 E expression at doses of 3.13 and 1.56 mg·mL~(-1), and the expression of HCoV-229 E nucleic acid was 9.47×10~5 and 9.47×10~6 copies/mL, respectively. Chaiyin Particles has a better effect on the mouse model with human coronavirus pneumonia with pestilence attacking the lung syndrome, and could play a role by enhancing immunity, and reducing inflammatory factor expression.

Background: Traditional Chinese exercises (TCEs) have a positive effect on glycemic control and hemoglobin A1c (HbA1c), but there is no consensus on the benefits of TCEs for patients with prediabetes., Objective: The objective of this study was to systematically investigate the effects of TCEs on blood glucose control in patients with prediabetes., Search Strategy: Comprehensive retrieval of randomized controlled trials (RCTs) was carried out using PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Data Knowledge Service Platform, China Biology Medicine disc, Google Scholar and Baidu academic databases. The retrieval window ranged from the establishment of the database to December 2018, and references related to the included trials were searched without language restrictions., Inclusion Criteria: The study included RCTs with a clinical diagnosis of prediabetes that was also treated with TCEs., Data Extraction and Analysis: Literature screening, data extraction and literature quality assessment were performed independently by two researchers. In the case of disagreement, a third party was invited to negotiate and make a decision. Standardized mean difference (SMD) was used to estimate the therapeutic effect. Meta-analysis was performed using Review Manager 5.3.5 and Stata 15.0. Heterogeneity was assessed using Q test and I 2 , and the source of heterogeneity was determined using Galbraith diagram and sensitivity analysis. A Q test resulting in P < 0.1 and I 2  > 50% indicated significant difference and random effect model analysis was performed. Otherwise, a fixed effect model was applied. Begg's and Egger's tests were used to assess publication bias., Results: Nine RCTs involving 485 participants were included in this study. The results showed that TCEs could reduce fasting blood glucose (FBG), 2 h blood glucose (2hPBG) and HbA1c in patients with prediabetes. The treatment subgroup showed that an intervention of 6 months had better results, while the Gongfa subgroup showed that the TCE Baduanjin yielded better results. (1) FBG: SMD = -0.73, 95% confidence interval (CI) [-0.97, -0.50], P < 0.00001; Baduanjin: SMD = -0.83, 95% CI [-1.13, -0.53], P < 0.00001; 6 month treatment: SMD = -0.73, 95% CI [-1.20, -0.26], P = 0.002. (2) 2hPBG: SMD = -0.75, 95% CI [-0.94, -0.57], P < 0.00001; Baduanjin: SMD = -0.62, 95% CI [-0.91, -0.32], P < 0.00001; 6 month treatment: SMD = -0.91, 95% CI [-1.39, -0.44], P = 0.0002. (3) HbA1c: SMD = -0.56, 95% CI [-0.89, -0.23], P = 0.00008; Baduanjin: SMD = -0.46, 95% CI [-0.83, -0.08], P = 0.02; 6 month treatment: SMD = -0.77, 95% CI [-1.24, -0.29], P = 0.002., Conclusion: TCEs had positive effects in improving blood glucose levels in patients with prediabetes. Hence, TCEs may be of potential therapeutic value for patients with prediabetes, as an adjuvant therapy along with other treatments. Although the evidence suggests that the intervention is effective for 6 months, the mechanism of TCEs on glycemic control, the minimum exercise dose and their safety remain to be further studied., (Copyright © 2020 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Although thought as a serotonin and norepinephrine reuptake inhibitor (SNRI), the antidepressant mechanisms of venlafaxine remain unknown. Previous reports have shown the role of peroxisome proliferator activated receptor α (PPARα) in depression. In this study, we investigated whether the antidepressant-like effects of venlafaxine require PPARα. We first examined whether repeated venlafaxine administration reversed the effects of chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) on PPARα in the hippocampus and medial prefrontal cortex (mPFC). Then, the pharmacologcial inhibitors of PPARα, GW6471 and MK886, were used to assay if the protecting effects of venlafaxine against chronic stress were prevented by PPARα blockade. Furthermore, gene knockdown of PPARα by AAV-PPARα-shRNA was also used. It was found that venlafaxine treatment fully restored the decreasing effects of CUMS and CRS on the hippocampal PPARα expression. Pharmacological inhibition of PPARα significantly attenuated the antidepressant-like effects of venlafaxine in mice. Moreover, gene knockdown of hippocampal PPARα also fully abolished the antidepressant-like actions of venlafaxine in mice. Collectively, hippocampal PPARα is an antidepressant target of venlafaxine., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Temporomandibular joint osteoarthritis (TMJOA) is a complex inflammatory condition with multiple factors and degenerative processes co-occurring. However, its pathogenesis remains uncertain. The purpose of the study was to observe the expression of Indian hedgehog (Ihh) signal related molecules in TMJOA induced by bite-raising and to study the effect and mechanism of Ihh signaling. Our research indicated that Ihh signaling pathway can be activated in condylar cartilage induced by bite-raising. The histological analysis showed TMJOA-like structural changes of condylar cartilage in experiment groups. Ihh, Smoothened (Smo), and Gli zinc finger transcription factors-1 (Gli-1) were activated in the experimental groups, and the expression levels increased significantly over time, whereas the sham control groups showed no fluctuation. Additionally, the expression levels of matrix metalloproteinase-13 (MMP-13) and cysteinyl aspartate specific proteinase-3 (Caspase-3) in the experiment groups increased in a time-dependent manner compared with the matched sham control groups. In conclusion, our results indicated that the Ihh signaling pathway may activate the occurrence of TMJOA by mediating the hypertrophy of chondrocytes, which may be an important regulatory mechanism and potential therapeutic target in the repair of condylar cartilage.

Background: Most allelochemicals are secondary products released from root excretions or plant residues that accumulate in continuous cropping systems and cause severe decline in peanut yield. Resveratrol is a plant-derived stilbene that is released from peanut residues and accumulates in the soil; however, its allelopathic effects on peanut production are overlooked. Effective management solutions need to be developed to relieve allelopathy caused by soil resveratrol. Here, the biodegradation of resveratrol by the fungal endophyte Phomopsis liquidambari was investigated in a mineral salt medium and a soil trial. Resveratrol and its metabolites (produced by degradation by P. liquidambari) were detected by high-performance liquid chromatography-mass spectrometry (HPLC-MS)., Results: Resveratrol released from peanut residues reached a maximum concentration of 0.18 μg g -1 soil in litterbag experiments. Exogenous resveratrol inhibited peanut growth, nodule formation, and soil dehydrogenase activity, and reduced the soil microbial biomass carbon content and bacterial abundance, indicating an allelopathic role in peanut growth. More than 97% of the resveratrol was degraded within 72 and 168 h by P. liquidambari in pure culture and soil conditions, respectively. Resveratrol was first cleaved to 3,5-dihydroxybenzaldehyde and 4-hydroxybenzaldehyde, which were subsequently oxidized into 3,5-dihydroxybenzoic acid and 4-hydroxybenzoic acid, respectively. Fungal resveratrol cleavage oxygenase and the related gene expression were enhanced when P. liquidambari was induced by the resveratrol during the incubation., Conclusion: Our results indicate that the practical application of the fungal endophyte P. liquidambari has strong potential for biodegrading soil resveratrol, which can cause allelopathy in peanut continuous cropping systems. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Chemotherapeutics are used extensively in cancer and encapsulating the drug in nanoparticles is an effective method to enhance therapeutic efficacy and reduce side effect. In this work, DOX-loaded chitosan nanoparticles were prepared using supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) from aqueous solution. The influences of solution concentration, CO 2 /solution ratio, mixer pressure, chitosan/DOX ratio and chitosan molecular weight on particle morphologies and sizes were investigated in detail. Well defined spherical nanoparticles with average diameter ranging from 120 nm to 250 nm were obtained, and the loading efficiency was up to 90%. FT-IR result showed that the structure of DOX was not changed after the SAA-HCM process. Zeta potential of the nanoparticles was about +50 mV. The in vitro drug release behavior conducted in the media with pH of 4.5, 6.5 and 7.4 respectively showed strongly pH responsive. In vitro cytotoxicity profiles revealed that the activity of DOX was well maintained after loaded into chitosan nanoparticles. The SAA-HCM process was demonstrated to be a promising technique for one-step production of polymer/drug composite nanoparticles suitable for cancer drug delivery from aqueous solution., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To explore the mechanism of lnc SNHG20 in the regulation of proliferation, invasion, and migration of breast cancer cells. mRNA levels of SNHG20, miR-495, and HER2 were detected by qRT-PCR. Protein level of HER2 was measured by Western blot. Cell proliferation, invasion, and migration were detected by CCK-8 assay, Boyden chamber assay, and Transwell assay. The combination between SNHG20 and miR-495 was confirmed by RNA pull down assay. The combination between miR-495 and HER2 was confirmed by luciferase report assays. We also established breast cancer-bearing mice model and analyzed tumor volumes. Our data showed SNHG20 expression was significantly upregulated, miR-495 expression was significantly downregulated, and HER2 expression was significantly upregulated in breast cancer tissues and cell lines. Besides, SNHG20 promoted the proliferation, invasion, and migration of breast cancer cells. We also found SNHG20 negatively regulated miR-495, and miR-495 could negatively regulate HER2. Moreover, we discovered that SNHG20 regulated HER2 via miR-495. SNHG20 regulated proliferation, invasion, and migration of breast cancer cells via miR-495/HER2. Finally, we confirmed the mechanism of SNHG20 in the regulation of proliferation, invasion, and migration in breast cancer-bearing mice model. SNHG20 regulates HER2 via miR-495 to promote proliferation, invasion, and migration of breast cancer cells., (© 2017 Wiley Periodicals, Inc.)

In this study, Paeonia suffruticosa roots and rhizospheric soil in five geographic regions which were harvested in October were utilized as experimental materials, then the diversity of endophytic and rhizospheric actinomycetes were investigated by High-throughput sequencing technique. The 1 754 operational taxonomic units (OTUs) were obtained from 129 954 high quality sequences, 1 311 OTUs were detected in rhizospheric actinomycetes and belonged to four classes, four orders, twenty-seven families and ninety-seven genera, thirty-three genera such as Ilumatobacter were found in the five regions rhizospheric soil while three genera such as Longispora were only detected in the Dao-di regions, the dominant genera were Mycobacterium, Nocardioides, Streptomyces. 443 OTUs were obtained in roots and distributed in three classes, three orders, twenty-four families and fifty genera, thirteen genera such as Cryptosporangium were found in the five regions roots while Planosporangium, Luteococcus were only detected in the Dao-di regions, the dominant genera were Nocardioides. Alpha diversity analysis showed that the Shannon and Chao1 index in rhizospheric actinomycetes in Bozhou, Tongling and Nanling region were higher than Heze and Luoyang. Based on principal co-ordinates analysis (PCoA) analysis, the rhizospheric actinomycetes formations were similar in Tongling and Nanling region, at the same in Tongling and Luoyang endophytic actinomycetes. According to heatmap analysis, Bozhou, Tongling and Nanling region rhizospheric actinomycetes showed a close similarity in actinomycetes community structures on phylogenetic analysis, while Tongling, Luoyang and Nanling endophytic actinomycetes showed the same. Our results not only suggested that the rich and diverse actinomycetes resources in P. suffruticosa roots and rhizospheric soil but also revealed rhizospheric actinomycetes in the Dao-di regions had high similarity., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Parathyroid hormone (PTH1-34)-loaded dry powders were fabricated from aqueous solution for pulmonary administration using supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM). Herein, chitosan oligosaccharide (CSO) was selected as a carrier in an effort to enhance transmucosal absorption of the drug. Well-defined, separated and spherical PTH(1-34)/CSO composite microparticles were obtained, and the particles size could be well controlled with narrow distribution. Aerodynamic performance was determined using next generation impactor (NGI), and the mass median aerodynamic diameter (MMAD) ranged strictly 1-5 μm range with fine particle fraction (FPF) up to 63.51%. The structural integrity of coprecipitated PTH(1-34) was validated by HPLC, FT-IR and circular dichroism, and a high loading efficiency up to 92.8% was obtained. TGA analyses revealed its thermal stability was preserved and XRD patterns showed amorphous structure of particles. The SAA-HCM process is proposed as a green technique for preparation of inhalable protein/polymer composite dry powders without use of any organic solvents., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Phenyllactic acid (PLA) is an important organic acid with wide antimicrobial activities against gram-positive and gram-negative bacteria and some fungi. This interesting compound can be synthesized by the microbial fermentation or the bioconversion using phenylpyruvic acid (PPA) as the key substrate and microorganisms as the whole-cell biocatalysts. However, the isolation of high-purity PLA with a high recovery from the crude fermentation or conversion broth is a challenging task. In this work, the separation of PLA from the crude conversion broth prepared by employing Lactobacillus buchneri cells as the whole-cell catalysts was achieved by the chromatography using the poly(hydroxyethyl methacrylate) (pHEMA)-based cryogel with a combination of anion-exchange and hydrophobic benzyl groups. The static adsorption behaviors of PLA under different salt concentrations and the adsorption capacities of PLA on the cryogel were measured experimentally. The chromatographic performance of PLA from the crude conversion broth was compared with that from the clarified broth. The results showed that the pHEMA-based cryogel has a high capacity of PLA, i.e., 14.64 mg mL -1 cryogel, and the adsorption of PLA was influenced by the salt concentration. By using deionized water as running buffer, PLA with a high purity of 97.6% was obtained with one step elution using 0.3 M NaCl as the elution solution with the recovery at the range of 80.2-90.8% from crude feedstock without any pretreatment at various flow velocities. These values were close to those obtained for the clarified broth, i.e., the purity of 98.4% and the recovery of 92.3% under the same chromatography conditions at 1 cm min -1 . The cryogel was then applied to separate PLA from clarified feedstock, high purity (>96.7%) and recovery (>91.4%) of PLA were found with 20 cycles, which verified the selectivity and robustness of prepared pHEMA-VBTAC cryogel. Therefore, the chromatography using pHEMA-based cryogel with the dual functional groups is an effective approach for the isolation of PLA directly from the crude bioconversion broth and thus could be interesting in the separation and production of high-purity PLA in industry., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Spontaneous cerebral spinal fluidotorrhea (SCSFO) is a type of CSF otorrhea without obvious causes including previous trauma, surgery, infection or neoplasm. The etiology of SCSFO remains unclear, the diagnosis can be overlooked because of the untypical clinical features. In this paper, we reviewed etiology, clinical features, diagnosis and therapy of SCSFO from recent relative literatures., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: The preoperative C-reactive protein/Albumin ratio (CAR) is valuable for predicting the prognosis of patients with various types of cancers. The aim of the present study is to investigate the prognostic value of the preoperative CAR and compare it with other systemic inflammatory response markers in patients with soft tissue sarcoma (STS)., Methods: This retrospective study included 206 patients with STS. The optimal cutoff value of the CAR was determined by receiver operating characteristic (ROC) analysis. The impact of the CAR and other clinicopathological features on overall survival (OS) and disease-free survival (DFS) was evaluated using univariate and multivariate Cox regression analyses. Kaplan-Meier survival analyses were used to compare groups classified by the CAR. Additionally, the area under the receiver operating characteristic curve (AUC) was used to compare the predictive ability of the CAR, high-sensitivity modified Glasgow prognostic score (Hs-mGPS), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR)., Results: The optimal cut-off value of the CAR was 0.1035 according to the ROC analysis. An increased CAR (≥0.1035) was significantly associated with older age, larger tumor size, deep tumor location, higher tumor grade and more advanced American Joint Committee on Cancer (AJCC) stage (all P<0.05). Patients with an elevated CAR (≥0.1035) exhibited a shorter median survival time and lower 5-year OS rate than those with a CAR<0.1035 (68.2 vs 115.8 months, P = 0.000; 44.6% vs 80.9%, P = 0.000, respectively). The results of a multivariate analysis indicated that the CAR (Hazard ratio (HR) 2.47, 95% confidence interval (CI) 1.47-4.14, P = 0.001) was an independent prognostic factor for OS along with tumor grade (P<0.05). Additionally, the CAR exhibited a greater AUC value (0.662) than the NLR and PLR, but the value was equal to the Hs-mGPS., Conclusions: The preoperative CAR is an independent prognostic factor predicting prognosis in STS and exhibits superior prognostic ability compared to the established inflammation-based prognostic indices., Competing Interests: CONFLICTS OF INTEREST None.

Objective: A micro-molecule peptide TP1623 of 99m Tc-human epithelial growth factor receptor 2 (HER2) was prepared and the feasibility of using it as a HER2-positive molecular imaging agent for breast cancer was evaluated., Methods: TP1623 was chemically synthesized and labeled with 99m Tc. The labeling ratio and stability were detected. HER2 expression levels of breast cancer cells (SKBR3 and MDA-MB-231) and cell binding activity were measured. Biodistribution of 99m TC-TP1623 in normal mice was detected. SKBR3/MDA-MB-231-bearing nude mice models with high/low expressions of HER2 were established. Tumor tissues were stained with hematoxylin-eosin (HE) and measured by immunohistochemistry to confirm the formation of tumors and HER2 expression. SPECT imaging was conducted for HER2-overexpressing SKBR3-bearing nude mice. The T/NT ratio was calculated and compared with that of MDA-MB-231-bearing nude mice with low HER2 expression. The competitive inhibition image was used to discuss the specific binding of 99m Tc- TP1623 and the tumor., Results: The labeling ratio of 99m Tc-TP1623, specific activity, and radiochemical purity (RCP) after 6 h at room temperature were (97.39 ± 0.23)%, (24.61 ± 0.06) TBq/mmol, and (93.25 ± 0.06)%, respectively. HER2 of SKBR3 and MDA-MB-231 cells showed high and low expression levels by immunohistochemistry, respectively. The in vitro receptor assays indicated that specific binding of TP1623 and HER2 was retained. Radioactivity in the brain was always at the lowest level, while the clearance rate of blood and the excretion rate of the kidneys were fast. HE staining showed that tumor cells were observed in SKBR3- and MDA-MB-231-bearing nude mice, with significant heteromorphism and increased mitotic count. The imaging of mice showed that targeted images could be made of 99m Tc-TP1623 in high HER2-expressing tumors, while no obvious development was shown in tumors in low HER2-expressing nude mice. No development was visible in tumors in competitive inhibition of imaging, which indicates the combination of 99m Tc-TP1623 and tumor was mediated by HER2., Conclusion: High labeling ratio and specific activity of 99m Tc-TP1623 is successfully prepared; it is a molecular imaging agent for HER2-positive tumors that has potential applicative value., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Programmed death ligand-1(PD-L1) functions as a negative mediator of immune response through different pathways in anti-tumor immunity. Recent studies have reported that PD-L1 plays a pivotal role in the function of regulatory T-cells (Tregs). Although increases in FOXP3+ Tregs infiltration and PD-L1 expression have been revealed in several cancers, their correlation with soft tissue sarcoma remains unknown. Methods: We included 163 cases of soft tissue sarcoma who were diagnosed and underwent extensive and radical resection at the Sun Yat-sen University Cancer Center, Guangzhou, China, from 2000-2010. PD-L1 and FOXP3 expression was evaluated by immunohistochemistry. Correlation between their expressions and associations with clinicopathological features were studied. Results: Among 163 STS samples, 19 (11.7%) exhibited PD-L1 positivity, and 41 (25.2%) cases expressed high FOXP3+ Treg infiltration. Significant correlation between PD-L1 expression and FOXP3+Treg infiltration in STS was identified (r=0.450, p<0.001). In univariate analysis, PD-L1 expression was significantly associated with high tumor grade and the age of patients, while the presence of FOXP3+ in tumor infiltrating Tregs was significantly associated with the age of patients, high tumor stage, higher tumor grade and tumor depth. Multivariate analysis revealed PD-L1 and FOXP3 as independent prognostic indicators significantly associated with OS and DFS. Conclusions: Our study revealed that PD-L1 and FOXP3+Tregs may work synergistically in promoting immune evasion of the tumors in soft tissue sarcoma. A combined strategy to block PD-L1/PD-1 with simultaneous depletion of Tregs may show promise in enhancing the therapeutic efficacy of these patients., Competing Interests: Competing Interests: We declare no conflicts of interest.

The loss of E-cadherin expression plays an important role in the development of endometriosis, but the molecular mechanism is not clear to date. It has been confirmed that the hypermethylation of the CpG island may be an important molecular mechanism in the transcriptional inactivation of E-cadherin gene (CDH1) in many cancers. The present study investigated the methylation status of CDH1 promoter region in ovarian endometriotic cysts and the endometrium of women with ovarian endometriosis. The results showed that the frequency of CDH1 promoter methylation in eutopic (26%), ectopic tissues (32%) of women with ovarian endometriosis was significantly higher than that of endometrium tissue of women without endometriosis (8%). Further, results of the study showed that the expression level of mRNA and protein of E-cadherin in methylation-positive tissues was significantly lower than that in methylation-negative tissues (p = 0.023 and 0.035, respectively). Pearson's correlation coefficients analysis showed the level of CDH1 mRNA expression was closely related to the level of E-cadherin protein expression. The results implied that the aberrant methylation of the CDH1 promoter region in the endometrium of the women may contribute, at least in part, to the development of ovarian endometriosis., (© 2016 S. Karger AG, Basel.)

Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) was proposed as a green technique to fabricate insulin-loaded dry powders for inhalation administration. N-trimethyl chitosan (TMC), a polymeric mucoadhesive absorption enhancer, was synthesized and successfully micronized from aqueous solution using SAA-HCM. The prepared well-defined spherical TMC microparticles with preserved structure and thermal stability were potential carriers for delivery of proteins. Then, insulin-loaded TMC microparticles with high loading efficiency were coprecipitated from aqueous solutions using SAA-HCM without use of any organic solvents. The polymer/protein ratio revealed to be a factor influencing the particle morphology, and non-coalescing composite microparticles in amorphous state mainly ranging from 1μm to 5μm could be obtained in this work. Aerodynamic properties were assessed by next generation impactor (NGI) and the mass median aerodynamic diameter (MMAD) lied inside the inhalable range of 1-5μm, while fine particle fraction (FPF) reached above 60%. The structural integrity of encapsulated insulin was confirmed by HPLC, circular dichroism and fluorescence spectroscopy. In vivo study demonstrated that TMC could enhance the absorption and bioavailability of the pulmonarily administered insulin formulation for SD rats. These results suggest that TMC microparticles could be efficiently prepared as a promising vehicle for drug delivery, and SAA-HCM is a promising technique to prepare inhalable polymer/protein composite dry powders., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Organic Light Emitting Diodes (OLEDs) has been a promising new research point that has received much attention recently. Emission in a conventional OLED originates from the recombination of carriers (electrons and holes) that are injected from external electrodes. In the device, Electrons, on the other hand, are injected from the Al cathode to an electron-transporting layer and travel to the same emissive zone. Holes are injected from the transparent ITO anode to a hole-transporting layer and holes reach an emitting zone through the holetransporting layer. Electrons and holes recombine at the emissive film to formsinglet excited states, followed by emissive light. It is because OLED is basically an optical device and its structure consists of organic or inorganic layers of sub-wavelength thickness with different refractive indices. When the electron and holes are injected through the electrodes, they combine in the emission zone emitting the photons. These photons will have the reflection and transmission at each interface and the interference will determine the intensity profile. The emissive light reflected at the interfaces or the metallic electrode returns to the emissive layer and affects the radiation current efficiency. Microcavity OLED can produce saturated colors and narrow the emission spetrum as a new kind of technique. In the paper, we fabricate microcavity OLED using glass substrate. Ag film acts as the anode reflector mirror; NPB serves as the hole-transporting material; Alq3 is electron-transporting material and organic emissive material; Ag film acts as cathode reflector mirror. The microcavity OLED structures named as A, B, C and D are glass/Ag(15 nm)/MoO3 (x nm)/NPB(50 nm)/Alq3 (60 nm)/A1(100 nm). Here, A, x = 4 nm; B, x = 7 nm; C, x = 10 nm; D, x = 13 nm. The characteristic voltage, brightness and current of these devices are investigated in the electric field. The luminance from the Devices A, B, C and D reaches the luminance of 928, 1 369, 2 550 and 2 035 cd x m(-2), respectively at 13 V. At 60 mA x cm(-2), the current efficiency of the microcavity OLEDs using MnO3 are about 2.2, 2.6, 3.1 and 2.6 cd x A(-2) respectively. It is found that electrons are majority carriers and holes are minority carriers in this microcavity OLEDs. MnO3 film can improve hole injection ability from 4 to 10 nm. In addition, hole injection ability is increased with the increasing thickness of the MnO3 film.

Endophytes were isolated and purified from the roots of medicinal plant Fengdan also known as Paeonia suffruticosa from Tongling region, Anhui province, China. Morphology and molecular biology methods were applied to indentify the endophyte strains. And methods of growth rate and filtering paper were also used for studying antibacterial/antifungal effects of the strains. As a result, 129 endophyte strains were isolated. Fifty-eight endophytic fungi strains were identified as 6 species in 4 genera and the dominant genus was Fusarium. Seventy-one endophytic bacteria strains were identified as 9 species in 3 genera and the dominant genus was Bacillus. Inhibitory diameter with endophytic fermenting liquid of Pseudomonas chlororaphis, F. nematophilum and B. megaterium from P. suffruticosa against Staphyloccocus aureus, Escherichia coli and B. subtilis reached 25.0,20.2,24.0 mm respectively. The inhibition rate of endophytic fermenting liquid from F. nematophilum against Penicillium sp. and Colletotrichum dematium reached 90.6% and 83.3%, respectively. The inhibition effect of P. chlororaphis against F. oxysporum f. sp. niveum and Mucor sp. was good and the antifungal rate reached 80.0% and 84.9%, respectively. P. suffruticosa in Tongling region contains abundant endophytes. P. chlororaphis and F. nematophilum are valuable species as starting strain about microbicide., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Background/aims: The function of BRAF V600E as a prognostic biomarker continues controversial by reason of conflicting results in the published articles., Methods: A systematical literature search for relevant articles was performed in PubMed, Cochrane Library, Google Scholar, Medline and Embase updated to August 5, 2015. The Chi-square test and I2 were employed to examine statistical heterogeneity. Pooled ORs with their corresponding 95% confidence intervals (95%CIs) were calculated to assess the relationship between clinicopathological features and BRAF(V600E) mutation. Subgroup analyses by ethnicity were also performed to explore the potential sources of heterogeneity. Furthermore, publication bias was detected using the funnel plot and all statistical analyses were conducted by the software of R 3.12., Results: Of 25,241 cases with PTC, 15,290 (60.6%) were positive for BRAF mutation and 9,951 (39.4%) were tested negative for BRAF mutation. Negative status of BRAF(V600E) mutation negative was significantly associated with gender (OR = 0.90, 95%CI = 0.83-0.97) and concomitant hashimoto thyroiditis (OR = 0.53, 95%CI = 0.43-0.64). By contrast, positive status of BRAF(V600E) mutation was a significant predictor of multifocality (OR = 1.23; 95%CI = 1.14-1.32), extrathyroidal extension (OR = 2.23; 95%CI = 1.90-2.63), TNM stage (OR = 1.67; 95%CI = 1.53-1.81), lymph node metastasis (OR = 1.67; 95%CI = 1.45-1.93), vascular invasion (OR = 1.47; 95%CI = 1.22-1.79) and recurrence/persistence (OR = 2.33; 95%CI = 1.71-3.18). However, there was no significant association between BRAF(V600E) mutation and factors including age > 45 (OR = 0.98; 95%CI = 0.89-1.07), tumor size (OR = 0.84; 95%CI = 0.64-1.09) and distant metastasis (OR = 1.23; 95%CI = 0.67-2.27)., Conclusion: This meta-analysis confirmed significant associations between BRAF(V600E) mutation and female gender, multifocality, ETE, LNM, TNM stage, concomitant hashimoto thyroiditis, vascular invasion and recurrence/persistence, suggesting the predictive value of BRAF(V600E) mutation for PTC prognosis., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

The aim of the present study was to investigate the clinical efficacy and safety of low-dose 90 Sr- 90 Y therapy combined with the topical application of 0.5% timolol maleate solution for the treatment of superficial infantile hemangiomas (IHs). A total of 72 infants with hemangiomas were allocated at random into the observation group (17 cases aged ≤3 months, 20 cases aged >3 months) or the control group (15 cases aged ≤3 months, 20 cases aged >3 months). The observation group was treated with low-dose 90 Sr- 90 Y combined with timolol, while the control group received an identical dose of 90 Sr- 90 Y with physiological saline. Data were collected for statistical analysis, and treatment efficacy was compared between the two groups. In the observation group, 100% (37/37) of subjects exhibited an 'excellent' response to the treatment, while 94.1% (16/17) of patients aged ≤3 months and 85.0% (17/20) aged >3 months were classed as being cured. In the control group, the treatment was classed as 'effective' in 100% (35/35) of the subjects, while the excellent response rate was 86.7% (13/15) among the infants aged ≤3 months and 75.0% (15/20) among the infants aged >3 months. The 'cure' rates in the control group were 66.7% (10/15) and 60.0% (12/20) for the ≤3-month- and >3-month-old subjects, respectively. The excellent response and cure rates were notably higher in the observation group than those in the control group. Comparison between the two groups revealed a χ 2 value of 13.90 (P<0.01) for excellent responses in subjects aged ≤3 months, while for patients aged >3 months the χ 2 value was 28.57 (P<0.01). Analysis of the cure responses gave similar results [≤3 months, χ 2 =23.22 (P<0.01); >3 months, χ 2 =15.67 (P<0.01)]. At 3-4 months after the first course of treatment, the cure rate was 33.3% (11/33) in the observation group, which was significantly higher than the rate of 18.32% (4/22) in the control group (χ 2 =5.92, P<0.05). No serious adverse reactions were observed in either group. In summary, low-dose 90 Sr- 90 Y therapy combined with the topical application of 0.5% timolol maleate induces a rapid response in superficial IH, with excellent efficacy and no obvious adverse reactions, and may represent a clinically applicable intervention.

Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) was used to prepare micrometric particles of a labile protein, i.e., trypsin from aqueous solution without use of any organic solvents. The trypsin particles precipitated had various morphologies under different process conditions, with particle diameters ranging from 0.2 to 4 μm. FTIR, SDS-PAGE, CD and fluorescence spectra were performed to analyze the structural stability of the protein, and trypsin retained above 70% of the biological activity. Besides, chitosan was selected as the polymer carrier in an effort to prepare trypsin composite microparticles via SAA-HCM process. The influences of chitosan molecular weight, polymer/protein ratio and solution concentration on the particle morphology and size distribution were investigated in detail. Non-coalescing spherical composite microparticles with a narrow particle distribution (0.2-3 μm) could be obtained. The SAA-HCM prepared particles were amorphous as demonstrated by XRD and had a loading efficiency about 90%. The protein release profiles of the composite microparticles were evaluated using both the immersion condition and a Franz diffusion cell. Finally, the distribution of the protein within the particles was characterized through CLSM analysis of FITC-labeled trypsin-loaded chitosan microparticles. The SAA-HCM process is demonstrated to be a protein-friendly and promising technique for production of protein and polymer/protein composite particles formulations from aqueous solutions for drug delivery systems., (Copyright © 2015 Elsevier B.V. All rights reserved.)