The efficacy and safety of chidamide, a new subtype-selective histone deacetylase (HDAC) inhibitor, have been demonstrated in a pivotal phase II clinical trial, and chidamide has been approved by the China Food and Drug Administration (CFDA) as a treatment for relapsed or refractory peripheral T cell lymphoma (PTCL). This study sought to further evaluate the real-world utilization of chidamide in 383 relapsed or refractory PTCL patients from April 2015 to February 2016 in mainland China. For patients receiving chidamide monotherapy (n = 256), the overall response rate (ORR) and disease control rate (DCR) were 39.06 and 64.45%, respectively. The ORR and DCR were 51.18 and 74.02%, respectively, for patients receiving chidamide combined with chemotherapy (n = 127). For patients receiving chidamide monotherapy and chidamide combined with chemotherapy, the median progression-free survival (PFS) was 129 (95% CI 82 to 194) days for the monotherapy group and 152 (95% CI 93 to 201) days for the combined therapy group (P = 0.3266). Most adverse events (AEs) were of grade 1 to 2. AEs of grade 3 or higher that occurred in ≥5% of patients receiving chidamide monotherapy included thrombocytopenia (10.2%) and neutropenia (6.2%). For patients receiving chidamide combined with chemotherapy, grade 3 to 4 AEs that occurred in ≥5% of patients included thrombocytopenia (18.1%), neutropenia (12.6%), anemia (7.1%), and fatigue (5.5%). This large real-world study demonstrates that chidamide has a favorable efficacy and an acceptable safety profile for refractory and relapsed PTCL patients. Chidamide combined with chemotherapy may be a new treatment choice for refractory and relapsed PTCL patients but requires further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0439-6) contains supplementary material, which is available to authorized users.
Due to the problematic degradation properties of plastics, the decomposition of plastic results in the formation of numerous microplastics (MPs), less than 5 mm in diameter. These MPs enter the soil and the ocean, eventually passing through the air, water, or food chain back to the human body and harming human health. In the last 80 years, male semen analysis parameters have shown a significant decline for unknown reasons, speculated to be caused by pollutants. No studies examined the relationship between human MP exposure and male infertility. In this article, we reviewed the relevant animal experimental research literature in recent years and calculated that the minimum human equivalent dose of MPs leading to abnormal male semen quality is 0.016 mg/kg/d. The literature comparison found that MP exposure in Japan and South Korea was close to this value. These results suggest that MPs can affect male semen quality and that MPs may significantly impact male fertility.
Presented here is the first reported case of natural killer (NK)/T-cell lymphoma associated with lactic acidosis (LA) and hypoglycemia. LA and hypoglycemia are rare complications of non-Hodgkin's lymphoma. A 28-year-old male patient with NK/T-cell lymphoma had a relapse after 14 mo of initial remission and was admitted to the hospital because of altered mental status. He developed severe LA (pH, 7.17; lactate, 11.2 mmol/L) and hypoglycemia (42 mg/dL) that was resistant to sodium bicarbonate and glucose infusions. A very brief partial remission was achieved after a cycle of vincristine, dexamethasone, and L-asparaginase was given, but the disease recurred quickly after chemotherapy was discontinued and the patient did not respond to additional chemotherapy. The patient expired at 47 d after relapse. An extensive review of the literature reveals that only 2 of 28 patients have achieved complete remission, and more than 75% of patients died within 1 mo. Furthermore, 90% of previously reported cases had liver involvement. The case described here indicates that non-Hodgkin's lymphoma-induced LA portends a poor prognosis.
Oligoasthenozoospermia is a complex disease caused by a variety of factors, and its incidence is increasing yearly worldwide. Yishen Tongluo formula (YSTLF), created by Professor Sun Zixue, has been used to treat oligoasthenozoospermia in clinical practice for several decades with a good therapeutic effect. However, the chemical and pharmacological profiles of YSTLF remain unclear and need to be elucidated. In this study, a network pharmacology approach was applied to explore the potential mechanisms of YSTLF in oligoasthenozoospermia treatment. All of the compounds in YSTLF were retrieved from the corresponding databases, and the bioactive ingredients were screened according to their oral bioavailability (OB) and drug-likeness (DL). The potential proteins of YSTLF were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, while the potential genes of oligoasthenozoospermia were obtained from the GeneCards database and the DisGeNET database. The STRING database was used to construct an interaction network according to the common targets identified by the online tool Venny for YSTLF and oligoasthenozoospermia. The topological characteristics of nodes were visualized and analyzed through Cytoscape. Biological functions and significant pathways were determined and analyzed using the Gene Ontology (GO) knowledgebase, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Metascape. Finally, the disease-formula-compound-target-pathway network was constructed by Cytoscape. A total of 106 bioactive ingredients and 134 potential targets from YSTLF were associated with oligoasthenozoospermia or considered to be therapeutically relevant. Pathway analysis indicated that the PI3K/Akt, MAPK and apoptosis signaling pathways were significant pathways involved in oligoasthenozoospermia. In conclusion, the current study expounded the pharmacological actions and molecular mechanisms of YSTLF in treating oligoasthenozoospermia from a holistic viewpoint. The potential molecular mechanisms were closely related to antioxidative stress, antiapoptosis and anti-inflammation, with TNF, CCND1, ESR1, NFKBIA, NR3C1, MAPK8, and IL6 being possible targets. This network pharmacology prediction may offer a helpful tool to illustrate the molecular mechanisms of the Chinese herbal compound YSTLF in oligoasthenozoospermia treatment.
The prevalence of varicoceles in male infertility is increasing; however, the exact mechanism is unknown, and no direct studies of varicose spermatic veins have been conducted. Three patients with varicocele infertility were included to explore the possible factors that cause varicocele infertility, and varicose and nearby normal veins were harvested by varicocelectomy. RNA sequencing was performed on six vascular samples, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the screened differential expressed genes which were validated by quantitative reverse transcription‐polymerase chain reaction. The genomes of the patients were analysed using next‐generation sequencing to screen for genetic factors behind varicocele infertility. 1171 genes were upregulated and 2772 were downregulated in varicose spermatic veins compared with those in normal veins. These genes were significantly enriched in the alcohol consumption pathway. HIST1H4C, HIST1H4F, HIST1H4K, TM9SF1, and TMEFF1 were significantly differentially expressed. The genomic results identified patients with mutations in CFTR, NANOS1, SRCAP, GATA4, GCM2, TUBB1, ALDH7A1, ANTXR1, and MAP3K1. In conclusion, our results indicated that Alcohol consumption may be a cause of varicoceles. Mutations in certain genes, such as CFTR, may be a cause of male infertility due to varicoceles.
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