OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

Objective:To investigate the effects of myeloid differentiation protein-2 (MD-2) on paclitaxel resistance cells in triple negative breast cancer (TNBC) through EGFR signaling pathway.Methods:Immunohistochemical method was used to detect the expression of MD-2 in cancer tissue and adjacent tissue of TNBC patients, and the relationship between MD-2 expression and clinicopathological parameters of patients was analyzed. The TNBC paclitaxel-resistant cell line was constructed and MD-2 expression in cells was interfered. Cell invasion was detected by Transwell, and cell apoptosis was detected by flow cytometry. The signaling pathways regulated by MD-2 were screened by transcriptome sequencing and verified by Western blot.Results:The expression of MD-2 was significantly enhanced in cancer tissues relative to adjacent tissues. High expression of MD-2 was closely related to clinical stage, tumor size, tumor recurrence and metastasis ( χ2=4.50, P=0.032; χ2=2.55, P=0.011; χ2=4.40, P=0.036). In cell experiments, compared with normal breast cells, the expression of MD-2 in TNBC cell lines was significantly enhanced. Compared with sh-NC group (100±11.52) (6.81±0.57), knockdown of MD-2 could inhibit the invasion (61.44±6.78) ( t=4.99, P=0.008) but promote apoptosis (15.19±1.06) ( t=12.06, P<0.001) of paclitaxel resistant TNBC cells. Transcriptome sequencing and Western blot results showed that MD-2 mainly affects the biological behavior of TNBC cells by regulating the EGFR signaling pathway. Conclusions:MD-2 promoted TNBC cell invasion and paclitaxel resistance, which may be achieved by affecting the EGFR signaling pathway. MD-2 is expected to become an effective target in TNBC treatment.

Tumor microenvironments (TMEs) are closely related to tumor resistance. TMEs are divided into cellular components and acellular components. The cellular components include tumor-associated macrophages, tumor-associated fibroblasts, mesenchymal stem cells, etc., which can enhance tumor resistance through recruitment and secretion of a variety of protective cytokines; acellular components such as extracellular matrix, hypoxia and acidification, etc., can mediate drug resistance by constructing physical barriers, affecting tumor cell growth and metabolism. Studying the mechanisms of TME-mediated drug resistance and reshaping TMEs can provide new strategies for anti-tumor therapy.

Objective:To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone (IRd) in Chinese patients with relapsed/refractory multiple myeloma (MM) .Methods:This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least. Ixazomib at an initial oral dose of 4 mg was administered. Seven patients had dose adjustment to 3 mg at the time of first dose. The lenalidomide doses were adjusted according to creatinine clearance rate. The efficacy and safety were evaluated every cycle.Results:In the study cohort of 74 patients, the median age was 65 years and 11 (14.9% ) patients received over three lines of therapy. Overall response rate (ORR) was 54.1% (40/74) , and 7 (9.5% ) , 14 (18.9% ) , and 19 (25.7% ) patients achieved stringent complete response or complete response, very good partial response, and partial response, respectively. The median progression-free survival and overall survival were 9.9 and 20 months, respectively. The median time to response was 1 month. The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study. The ORR of patients refractory to bortezomib, lenalidomide, and bortezomib plus lenalidomide were 52.0% (13/25) , 57.1% (4/7) , and 33.3% (6/18) , respectively. The rate of grade 3-4 adverse events was 36.5% (27/74) . Common hematological toxicities were anemia, thrombocytopenia, lymphopenia, and neutropenia. Common non-hematological toxicities were fatigue, gastrointestinal symptoms, and infections. Two cases of grade 3 peripheral neuropathy were reported. The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients [77.8% (14/18) vs 46.4% (26/56) , P=0.020]. There was no difference in the rate of grade 3-4 adverse events [33.3% (6/18) vs 37.5% (21/56) , P=0.749]. Conclusion:The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.

Objective: To analyze effect of fractured file removal from the middle third root canal on root fracture resistance using finite element analysis, which provides a theoretical basis for clinical prognosis evaluation. Methods: Two finite-element models were established, the fractured file removal model (fractured file located in the middle third of root canals, followed by ultrasonic file removal and root canal preparation) and the control model (root canal preparation only), and compressive displacement dependencies on compressive force was computed and compared with experimental data for validation. The validated finite-element models were used to analyze the stress distribution differences during the initiation, propagation and completion of the crack between fractured file removal specimen and control one. Results: The critical breaking force of the fractured file removal specimen was 406 N, and the finite element simulation result was 396 N. The critical breaking force of the control specimen was 502 N, and the finite element simulation result was 483 N. The position of crack initiation in the finite element simulation was basically consistent with that in the experiment. The experimental data of compressive test and the results of finite-element computation were in agreement, thus validating the finite-element model. In the process of continuous pressure, the stress distribution of the control root is relatively uniform, and the location of crack initiation and the direction of propagation have a certain unpredictability. Compared with the control root, the stress concentration on the root with fracture file removal was obvious, especially on edges, and the number of cracks are much more. Because of the thinner radicular wall, the crack propagation rate is faster too. Therefore, the overall root fracture resistant is decreased obviously. Conclusions During the fractured file removal procedure, amount of dentine removed should be minimized, and the edges and corners which caused by fractured file removal should be shaped to smooth in order to reduce the stress concentration and prevent the root from fracture.

Objective To investigate effect of Salvia miltiorrhiza Ligustrazine on peripheral lymphocyte neutrophil proportion, neurological function score and prognosis in patients with acute cerebral infarction. Methods 125 cases of acute cerebral infarction in our hospital from June 2015 to June 2016 were selected as the research object, randomly divided into two groups, the control group was treated with conventional treatment of acute cerebral infarction, patients in the observation group in the control group patients on the basis of Salviae Miltiorrhizae and Ligustrazine Hydrochloride Injection, all patients were detected in the blood leukocyte classification, and the NIHSS evaluation of patients with neurological function and prognosis of the two groups of patients. Results After treatment, the observation group of white blood cells in patients with (×109/L), neutrophil (%), neutrophil / lymphocyte was significantly lower than the control group patients, two groups of patients before treatment, after treatment of 1 day and 7 days, two groups of NIHSS score comparison showed no significant difference, after the treatment of 14d patients in the observation group the NIHSS score was (11.1±3.3), which was obviously lower than the control group, the patients in the observation group were six cases death and disability in three cases, 53 cases of independent life, significantly better than the control group, the difference was statistical significance(P<0.05). Conclusion Salvia miltiorrhiza Ligustrazine can help to reduce the ratio of neutrophil / lymphocyte, improve neurological function and improve the prognosis of patients with acute cerebral infarction, and it is worthy of clinical application.

Toxascaris leonina is a common parasitic nematode of wild mammals and has significant impacts on the protection of rare wild animals. To analyze population genetic characteristics of T. leonina from South China tiger, its mitochondrial (mt) genome was sequenced. Its complete circular mt genome was 14,277 bp in length, including 12 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 2 non-coding regions. The nucleotide composition was biased toward A and T. The most common start codon and stop codon were TTG and TAG, and 4 genes ended with an incomplete stop codon. There were 13 intergenic regions ranging 1 to 10 bp in size. Phylogenetically, T. leonina from a South China tiger was close to canine T. leonina. This study reports for the first time a complete mt genome sequence of T. leonina from the South China tiger, and provides a scientific basis for studying the genetic diversity of nematodes between different hosts.
Animals ; Animals, Wild ; Bias (Epidemiology) ; China* ; Codon, Initiator ; Codon, Terminator ; DNA, Intergenic ; Genes, rRNA ; Genetic Variation ; Genome ; Genome, Mitochondrial* ; Mammals ; Phylogeny ; RNA, Transfer ; Sequence Analysis* ; Tigers* ; Toxascaris*

ObjectiveTo investigate the predisposing factors and pathogenic fungal species of Malassezia folliculitis in different geographical areas and body sites.MethodsTotally,241 patients diagnosed with Malassezia folliculitis were asked to complete a questionnaire.The content of hair follicles was obtained and subjected to fungal smear and culture examination.Fungal species were identified according to morphological,physiological and biochemical features.Results Of the 241 patients with Malassezia folliculitis,204 (84.65％) were positive for smear examination.A total of 259 specimens were collected from these patients,and fungal culture grew 213(82.24％) strains,of which,209 belonged to Malassezia species,4(1.54％) to Candida species.Among the 209 Malassezia strains,186 were activated and subjected to species identification which resulted in 6 species,including M.furfur (111 strains,59.68％ ),M.sloofiae (43 strains,23.12％ ),M.sympodialis (17 strains,9.14％),M.globosa (9 strains,4.84％),M.pachydermatis (4 strains,2.15％),and M.obtuse(2 strains,1.08％ ).Of the pathogenic fungi of Malassezia folliculitis,M.furfur predominated in the chest,back,abdomen,face and neck,M.sloofiae in the upper limbs,shoulders and vertex,M.globosa in the lower limbs.There were obvious differences in the distribution of pathogenic fungal species at different body sites in a same host,and M.furfur with M.sloofiae or M.sympodialis appeared to be the most common pathogens.ConclusionsIn this study,6 Malassezia species are identified in patients with Malassezia folliculitis in Nantong and Nanjing area,M.furfur and M.sloofiae appear to be the dominant pathogens.

Objective To compare broth microdilution and agar dilution methods for in vitro testing of activities of fluconazole,ketoconazole and itraconazole against clinical Malassezia isolates.Methods Broth microdilution and agar dilution methods were used to determine the minimal inhibitory concentration(MIC)of fluconazole,ketoconazole and itraconazole for 27 clinical strains(5 species)of Malassezia.Results The minimal inhibitory concentration(MIC)ranges of fluconazole,ketoconazole and itraconazole were 0.25-≥64 mg/L,≤0.03-0.5 mg/L and ≤0.03-0.125 mg/L respectively as shown by broth microdilution method,2-≥64 mg/L,≤0.03-0.5 mg/L and ≤0.03-0.25 mg/L respectively as revealed by agar dilution method.Both methods demonstrated that itraconazole possessed the strongest activity against Malassezia species,followed by ketoconazole and fluconazole.The agreement rate in MICs between the two methods was 78.8％,85.2％ and 88.9％,respectively for fluconazole,ketoconazole and itraconazole,with the intraclass correlation coefficients (ICCs)being 0.88,0.80 and 0.76 respectively.Conclusions Fluconazole,ketoconazole and itraconazole are highly active against Malassezia species in vitro,and itraconazole is the most active.Broth microdilution and agar dilution method coincide well in,and are applicable for,the antifungal susceptibility testing of Malassezia species in vitro.

Objective To determine the extracellular enzymatic activity of common pathogens for onychomycosis, in the hope of finding virulence factors associated with the pathogenesis of onychomycosis. Methods Strains tested in this study included standard strains of common dermatophyte and non-dermatophyte fungi as well as clinical isolates of Trichophyton rubrum from patients with onychomycosis. All the tested strains were cultured in medium containing nail fragments at 25 ℃ for 10 to 21 days followed by the determination of the nail fragment-containing medium, a significant increase was observed in the activities of esterase, esterase lipase, N-acetyl-β-glucosaminidase and α-mannosidase in dermatophytes compared with non-dermatophytes (all P ＜ 0.05 ), as well as in the activity of N-acetyl-β-glucosaminidase in Trichophyton rubrum compared with the other tested species of fungi (all P ＜ 0.05). No significant difference was noted in the activity of extracellular enzymes, except for that of naphthol-AS-BI-phosphohydrolase, between the isolates of Trichophyton rubrum from patients with different ranges of scoring clinical index for onychomycosis (SCIO). Conclusions In specific conditions, the extracellular enzymatic activity of fungi isolated from patients with onychomycosis is associated with fungal species, and may have a certain influence on the manifestations of anychomycosis.