[Effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source in Sichuan Province from 2010 to 2022].

OBJECTIVE: To evaluate the effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source in Sichuan Province from 2010 to 2022, so as to provide insights into formulation of future control interventions. METHODS: Data pertaining to comprehensive echinococcosis control measures with emphasis on management of infectious source and echinococcosis surveillance in Sichuan Province from 2010 to 2022 were collected. The effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source was evaluated with prevalence of human echinococcosis, detection of newly diagnosed echinococcosis patients, prevalence of Echinococcus infection in domestic dogs, prevalence of cystic echinococcosis in livestock, prevalence of alveolar echinococcosis in small mammals and awareness of echinococcosis control knowledge, and Spearman's rank correlation analysis. RESULTS: The prevalence of human echinococcosis reduced from 1.08% in 2010 to 0.40% in 2022 in Sichuan Province (χ2 = 1 482.97, P < 0.05), with a reduction from 0.30% to 0.02% in the detection of newly diagnosed echinococcosis cases (χ2 = 2 776.41, P < 0.05), a reduction from 15.87% to 0.46% in the prevalence of Echinococcus infection in domestic dogs (χ2 = 20 823.96, P < 0.05), a reduction from 8.05% to 1.07% in the prevalence of cystic echinococcosis in livestock (χ2 = 1 296.02, P < 0.05), and the awareness of echinococcosis control knowledge increased from 50.65% to 95.24% (χ2 = 34 938.63, P < 0.05); in addition, there was a year-specific prevalence rate of alveolar echinococcosis in small mammals (χ2 = 164.07, P < 0.05). Spearman's rank correlation analysis revealed that the detection of newly diagnosed echinococcosis cases correlated positively with the prevalence of Echinococcus infections in domestic dogs (rs = 0.823, P < 0.05) and the prevalence of cystic echinococcosis in livestock (rs = 0.795, P < 0.05), and correlated negatively with the awareness of echinococcosis control knowledge (rs = - 0.918, P < 0.05), and the prevalence of Echinococcus infection in domestic dogs correlated positively with the prevalence of cystic echinococcosis in livestock (rs = 0.753, P < 0.05) and negatively with the awareness of echinococcosis control knowledge (rs = -0.747, P < 0.05); however, there was no correlation between the prevalence of Echinococcus infections in domestic dogs and the prevalence of alveolar echinococcosis in small mammals (rs = -0.750, P > 0.05). CONCLUSIONS: The comprehensive echinococcosis control measures with emphasis on management of infectious source had achieved remarkable effectiveness in Sichuan Province; however, the transmission chain of echinococcosis has not been interrupted. Reinforced comprehensive echinococcosis control measures with emphasis on management of infectious source and sustained tracking evaluation of the effectiveness are recommended in Sichuan Province.

[Effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022].

OBJECTIVE: To evaluate the effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, so as to provide insights into echinococcosis control. METHODS: Administrative villages were sampled using a multi-stage cluster random sampling method from Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, and all residents at ages of 12 years and older in the sampled villages were screened for echinococcosis, and schools were sampled using a cluster sampling method, and all children at ages of 12 years and older in the sampled schools were screened for echinococcosis. Domestic dogs were sampled using a systematic random sampling method, and one domestic dog stool sample was collected from each household. Stray dog stool samples were collected outside the villages, and Echinococcus coproantigens were detected using enzyme-linked immunosorbent assay in domestic and stray dogs. In addition, echinococcosis was screened in sheep and cattle in designated slaughterhouses in Tianzhu Tibetan Autonomous County. The trends in the prevalence of echinococcosis in humans and livestock and the positive rate of Echinococcus coproantigens in dogs were examined with the Cochran-Armitage trend test. In addition, individuals screened for echinococcosis were randomly sampled from 2007 to 2022 for survey on the awareness of echinococcosis control knowledge. RESULTS: A total of 290 356 person-times were screened for echinococcosis among residents at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 094 residents detected with cystic echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ2 = 358.602, P < 0.001). A total of 32 931 person-times were screened for echinococcosis among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 296 children detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ2 = 267.673, P < 0.001). A total of 33 230 domestic dog stool samples were tested for Echinococcus coproantigens in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 777 Echinococcus coproantigens-positive samples tested, and the positive rate of Echinococcus coproantigens appeared a tendency towards a decline in domestic dogs over years (χ2 = 2 210.428, P < 0.001), while the positive rate of Echinococcus coproantigens showed a tendency towards a rise in domestic animals from 2016 to 2022 (χ2 = 37.745, P < 0.001). The positive rate of Echinococcus coproantigens remained relatively stable in stray dogs in Tianzhu Tibetan Autonomous County, Gansu Province from 2019 to 2022 (χ2 = 0.315, P = 0.575). A total of 10 973 sheep were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2007 to 2022, with 334 sheep detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a decline in sheep over years (χ2 = 53.579, P < 0.001); however, there was no significant change in the detection of echinococcosis during the period from 2015 through 2022 (χ2 = 1.520, P = 0.218). A total of 2 400 cattle were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2017 to 2022, with 231 cattle detected with echinococcosis, and the detection of echinococcosis showed a tendency towards a decline over years (χ2 = 5.579, P < 0.05). The awareness of echinococcosis control knowledge increased from 44.37% in 2007 to 94.00% in 2022 among residents at ages of 12 years and older and from 52.50% in 2007 to 92.50% in 2022 among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, respectively. CONCLUSIONS: There has been a reduction in the detection of echinococcosis in humans and domestic animals and the positive rate of Echinococcus coproantigens in dogs and a rise in the awareness of the echinococcosis control knowledge following the implementation of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province; however, integrated echinococcosis control measures are still required for further control of the prevalence of echinococcosis.

[Prevalence of Echinococcus infections in wild carnivores based on copro - DNA tests in Serthar County of Sichuan Province].

OBJECTIVE: To investigate the prevalence of Echinococcus infections in wild carnivores in Serthar County, Sichuan Province, so as to provide insights into echinococcosis control in local areas. METHODS: Stool samples were collected from wild carnivores in Serthar County, Sichuan Province in May 2021, and the host sources of stool samples and Echinococcus infections were identified using PCR assays. The prevalence of E. multilocularis, E. granulosus and E. shiquicus infections was estimated in different hosts. RESULTS: A total of 583 stool samples were collected from wild carnivores, including 147 stool samples from fox, 154 from wolf, 227 from wild dogs and 11 from lynx. The overall prevalence of E. multilocularis, E. granulosus and E. shiquicus infections was 5.68%, 0.19% and 14.20% in canine stool samples, and no E. granulosus infection was detected in fox stool samples, while the prevalence of E. multilocularis and E. shiquicus infections was 0.68% and 47.62% in fox stool samples (χ2 = 88.41, P < 0.001). No E. granulosus or E. shiquicus infection was detected in wolf stool samples, and the prevalence of E. multilocularis infection was 10.39% in wolf stool samples. The prevalence of E. multilocularis, E. granulosus and E. shiquicus infections was 5.73%, 0.44% and 2.20% in canine stool samples (χ2 = 12.13, P < 0.01). In addition, the prevalence of E. multilocularis infections was significantly higher in wolf stool samples than in canine and fox stool samples (χ2 = 13.23, P < 0.01), and the prevalence of E. shiquicus infections was significantly higher in fox stool samples than in canine and wolf stool samples (χ2 = 187.01, P < 0.001). No Echinococcus infection was identified in 11 lynx stool samples. CONCLUSIONS: The prevalence of Echinococcus infections is high in wild canines in Serthar County, Sichuan Province. Wolf, wild dog and fox all participate in the wild life cycle of E. multilocularis in Serthar County, and wolf and wild dogs may play a more important role.

[Prevalence of Echinococcus infection in small mammals captured from Shiqu County, Sichuan Province from 2015 to 2020].

OBJECTIVE: To investigate the prevalence of Echinococcus infection in small mammals in Shiqu County, Sichuan Province from 2015 to 2020, so as to provide insights into echinococcosis control in Shiqu County. METHODS: One setting with frequent activity of small mammals was sampled as the survey site from each of 9 townships where human alveolar echinococcosis was hyperendemic, in Shiqu County, Sichuan Province from 2015 to 2020. Two quadrats measuring 50 m × 50 m were assigned in each survey site during the period between July and August from 2015 to 2020 to capture all small mammals in quadrats, and the species of small mammals were identified by morphological characteristics. All captured small mammals were dissected in the field and Echinococcus infection was identified by visual examinations. The affected organs of Echinococcus - infected small mammals were collected, and Echinococcus infection was detected using PCR assay, with Echinococcus species characterized. The prevalence of Echinococcus infection was calculated in small mammals, and the trends in the prevalence of Echinococcus infection were analyzed during the period from 2015 to 2020. In addition, the prevalence of Echinococcus infection was compared in small mammals using visual examinations and PCR assay. RESULTS: A total of 2 692 small mammals were captured in the survey sites of Shiqu County from 2015 to 2020, and morphology characterized 1 360 Microtus fuscus (50.52%) and 1 332 Plateau pika (49.48%). The prevalence rates of Echinococcus infection were 35.63%, 19.16%, 21.41%, 8.40%, 7.68% and 4.44% by visual examinations and 18.96%, 5.36%, 5.61%, 4.58%, 3.30% and 0.37% by PCR assay in small mammals in Shiqu County from 2015 to 2020, both showing a tendency towards a decline year by year (χ2 = 215.024 and 117.045, both P values < 0.001). The prevalence of Echinococcus infection was significantly higher in small mammals by visual examinations than by PCR assay during the period from 2015 to 2020 except in 2018 (χ2= 33.597, 21.815, 51.373, 17.268 and 9.537, all P values < 0.01). PCR assay detected a reduction in the prevalence of E. multilocularis infection from 10.21% to 0.37% and a reduction in the prevalence of E. shiquicus infection from 8.75% to 0 in small mammals in Shiqu County from 2015 to 2020, both appearing a tendency towards a decline year by year (χ2 = 117.045 and 43.436, both P values < 0.001). In addition, the prevalence of E. multilocularis and E. shiquicus infections reduced from 15.19% to 0.45% and from 8.23% to 0 in M. fuscus, and the prevalence of E. multilocularis and E. shiquicus infections reduced from 7.76% to 0 and from 9.01% to 0 in P. pika in Shiqu County from 2015 to 2020. CONCLUSIONS: M. fuscus and P. pika were dominant species of small mammals in Shiqu County, Sichuan Province from 2015 to 2020, and E. multilocularis infection was mainly found in M. fuscus and E. shiquicus infection mainly found in P. pika. The prevalence of Echinococcus infection appeared a tendency towards a decline in both M. fuscus and P. pika year by year during the period from 2015 to 2020.

[Analysis of the equity of health human resource allocation for echinococcosis control based on Gini index].

OBJECTIVE: To analyze the current status and evaluate the equity of health human resource allocation for echinococcosis control in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, so as to provide the empirical evidence for optimizing the health human resource allocation for echinococcosis control. METHODS: A questionnaire survey was performed to collect the numbers of health human sources for echinococcosis control, including health workers, healthcare professionals, certified/assistant physicians and registered nurses, per 1 000 permanent residents, per 1 000 m2, per 1 000 residents screened using Bmode ultrasonography and per 1 000 echinococcosis patients in two highly endemic counties and three lowly endemic counties in Ganzi Tibetan Autonomous Prefecture, Sichuan Province from 2016 to 2019. The equity of health human resource allocation for echinococcosis control was evaluated by permanent residents and geographical areas using Lorenz curve and Gini index in Ganzi Tibetan Autonomous Prefecture from 2016 to 2019. RESULTS: The numbers of health workers, healthcare professionals, certified/assistant physicians and registered nurses per 1 000 permanent residents, per 1 000 permanent residents, per 1 000 m2, per 1 000 residents screened using B-mode ultrasonography and per 1 000 echinococcosis patients were 0.99-, 1.06-, 1.78- and 1.88-fold; 3.38-, 3.67-, 6.00- and 6.00-fold; 1.64-, 1.74-, 3.22- and 3.18-fold; and 64.92-, 70.39-, 139.34- and 117.44-fold more in lowly endemic counties than in highly endemic countries in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, 2019. The Gini indexes of health human resource allocation for echinococcosis control were 0.371 to 0.397 by permanent residents and 0.477 to 0.591 by geographical areas in Ganzi Tibetan Autonomous Prefecture from 2016 to 2019, and the Gini indexes (0.469 to 0.730) for allocation of certified/assistant physicians and registered nurses were both higher than those of health workers and healthcare professionals (0.302 to 0.451) by both permanent residents and geographical areas. CONCLUSIONS: The health human resource allocation for echinococcosis control showed general equity by permanent residents and poor equity by geographical areas in Ganzi Tibetan Autonomous Prefecture, Sichuan Province from 2016 to 2019.

[Epidemiology of echinococcosis in Serthar County of Sichuan Province in 2019].

OBJECTIVE: To investigate the epidemiology of echinococcosis in Serthar County, Sichuan Province, so as to provide insights into optimization of echinococcosis control measures. METHODS: The prevalence of human echinococcosis was surveyed among permanent residents living in Serthar County at ages of over 2 years from 2016 to 2019, and the prevalence of Echinococcus infections was surveyed in owned dogs, yaks and rodents in 2019. The epidemiological features of echinococcosis in humans and animals were descriptively analyzed. RESULTS: The overall prevalence of human echinococcosis was 3.72% (1 613/43 362) in Serthar County from 2016 to 2019, and the prevalence rates of cystic echinococcosis, alveolar echinococcosis and mixed infections of cystic echinococcosis and alveolar echinococcosis were 1.72% (745/43 362), 1.98% (860/43 362) and 0.02% (8/43 362), respectively. The prevalence of human echinococcosis was higher in pastoral areas (4.13%, 1 577/38 149) than in semi-agricultural and semi-pastoral areas (0.69%, 36/5 213) (χ2 = 151.82, P < 0.05); however, there was no significant difference in the prevalence between men (3.76%, 819/21 787) and women (3.68%, 794/21 575) (χ2 = 0.19, P > 0.05). Cystic echinococcosis was the predominant type in students with echinococcosis (93.78%, 422/450), while alveolar echinococcosis was the predominant type in herders with echinococcosis (72.16%, 801/1 110). There was a significant difference in the constituent ratio of echinococcosis types between students and herders (χ2 = 588.57, P < 0.05). In addition, higher prevalence of echinococcosis was detected in nomadic populations (4.58%, 1 008/22 021) than in community-dwelling populations (2.83%, 605/21 341) (χ2 = 91.88, P < 0.05). The Echinococcus copro-antigen-positive rate was 0.19% (4/2 157) in owned dogs, and the detection rate of echinococcosis was 8.00% (16/200) in yaks and 3.10% (31/1 000) in rodents in 2019. CONCLUSIONS: Echinococcosis is highly prevalent in Serthar County, Sichuan Province. Sustained management of source of Echinococcus infections, improved treatment of echinococcosis patients and timely health education for nomadic populations are recommended.

[Frequency properties of bone-conducted vibration and sound-induced ocular evoked myogenic potential].

Objective: The present study was to compare the frequency characteristics of bone- conducted vibration (BCV) and air-conducted sound-induced ocular vestibular evoked myogenic potential(oVEMP) with different stimulation settings, so as to select an optimal setting. Methods: Bruel and Kjaer artificial mastoid was used to calibrate bone vibrator, the mini-shaker. The outputspectrum and transient waveform were recorded when the input frequency was set at different frequencies and data were further analyzed to get the peake quivalent force level value of the output vibration. oVEMP was recorded as we previously reported with normal young adults. Response prevalence, latency, wave interval, amplitude, amplitude ratio, and bilateral amplitude asymmetry ratio were recorded and analyzed. SPSS 24.0 software was used for statistical analysis. Results: Output peak equivalent force level increased as the intensity of primary input stimulation increased at certain frequency,while it decreased as the frequency of primary input stimulation increased at certain intensity. Peak equivalent force level of 500 Hz tone burst (1-2-1) input stimulation was greatest as 139.8 dB when using mini-shaker for vibration stimulation,even greater when using bone conductor B-71.Twenty subjects were elicited with normal oVEMP with N1 and P1 waves in both ears using air-conducted stimulation or bone-conducted vibration.The response rate in these subjects was 95% and 100% respectively. The latency of N1 was (11.33±1.35) ms and (10.14±0.38) ms, latency of P1 was (16.24±1.56) ms and (15.65±1.19) ms, interval N1-P1 was (4.59±1.26) ms and (5.55±0.81) ms, symmetry coefficient was 12.22%[5.50%,21.85%] and 8.74%[3.37%,14.08%], amplitude was 3.07[2.05,4.43] µV and 3.07[2.05,4.43] µV in sound and bone conducted vibration group, respectively. The latency of N1, latency of P1, interval N1-P1, symmetry coefficient and n1-P1 amplitude of BC-oVEMP were different statistically (all P<0.05). Conclusions: 500 Hz 45 dB input stimulation setting is the optimal parameter for BC-oVEMP. BC-oVEMP can be recorded simply, safely and quickly in normal young people, thus it is a clinically practical way of measuring utricular function.

USP3 promotes proliferation of non-small cell lung cancer through regulating RBM4.

OBJECTIVE: Previous studies have shown that ubiquitin specific protease 3 (USP3) is an oncogene. However, the role of USP3 in non-small cell lung cancer (NSCLC) has not been reported. This study aims to explore the expression characteristics of USP3 in NSCLC, and its regulation on the proliferative capacity of NSCLC cells. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression levels of USP3 and RNA Binding Motif 4 (RBM4) in 42 pairs of tumor tissues and adjacent tissue specimens collected from NSCLC patients. Meanwhile, the correlation between the messenger ribonucleic acid (mRNA) expressions of USP3 and RBM4, and the clinical indicators and prognosis of NSCLC patients were analyzed. At the same time, mRNA expression of USP3 in NSCLC cell lines was further verified by the qRT-PCR method. In addition, USP3 knockdown and overexpression models were constructed using lentivirus in NSCLC cell lines H1299 and SPCA1. Cell counting kit-8 (CCK-8), cell colony formation, and 5-Ethynyl-2'-deoxyuridine (EDU) assays were performed to evaluate the influence of USP3 on proliferative capacity in NSCLC cells. Finally, Dual-Luciferase reporter assay and rescue experiments were conducted to further explore its underlying molecular mechanism. RESULTS: In this experiment, qRT-PCR results revealed that the expression level of USP3 in tumor tissues of NSCLC patients was remarkably higher than that in adjacent tissues, and the difference was statistically significant. Compared with NSCLC patients with low expression of USP3, those with high USP3 expression suffered much more advanced pathology stage and lower overall survival rate. Proliferation ability of NSCLC cells overexpressing USP3 was remarkably enhanced, while the opposite result was observed in the USP3 knockdown group. Subsequently, RBM4 expression in NSCLC tissue samples was found to be significantly reduced and negatively correlated with USP3 level. In addition, the result of Dual-Luciferase reporter assay demonstrated that USP3 can be targeted by RBM4. Rescue experiments revealed that RBM4 was responsible for NSCLC progression regulated by USP3. CONCLUSIONS: The above studies indicated that USP3 expression was remarkably up-regulated in NSCLC tissues, which was closely related to the pathological staging and poor prognosis of NSCLC patients. Therefore, USP3 might accelerate the proliferation of NSCLC cells via regulating RBM4.

Prognostic value of the pretreatment albumin:globulin ratio combined with adult comorbidity evaluation 27 and TMN staging in patients with squamous cell carcinoma of the maxillary sinus.

The albumin:globulin (A:G) ratio, adult comorbidity evaluation 27 (ACE-27), and TMN staging have been shown to be strong predictive indicators of the survival of patients with many types of tumours. We have investigated the prognostic value of pretreatment based on the A:G ratio combined with TMN staging and ACE-27 in patients with squamous cell carcinoma (SCC) of the maxillary sinus. We studied 196 patients, and the prognostic value was explored by univariate and multivariate Cox's hazards analysis. Multivariate analyses suggested that pretreatment A:G ratio was independently associated with overall survival (hazard ratio (HR) 1.542, 95% CI 1.219 to 1.991, p=0.002); disease-specific survival, (HR 1.499, 95% CI 1.197 to 1.842, p=0.001); and disease-free survival (HR 1.452, 95% CI 1.207 to 1.834, p<0.001). Additional prognostic factors shown in the survival analyses included ACE-27, pathological T stage, and pathological N stage. Pretreatment A:G ratio combined with ACE-27 and TMN staging were powerful prognostic indicators of outcome in patients with SCC of the maxillary sinus, which has potentially important ramifications for stratification of the disease in the future.

[Risk factors of human cystic echinococcosis in Shiqu County Sichuan Province: a case-control study].

OBJECTIVE: To identify the main risk factors of human cystic echinococcosis in Shiqu County, Sichuan Province, so as to provide the reference for the formulation of echinococcosis control strategies in Shiqu County. METHODS: During the period from November 2015 through June 2017, the patients with cystic echinococcosis (case group) and healthy controls (control group) were randomly sampled from Shiqu County as the study subjects. A questionnaire survey was conducted to capture the study subjects'age, gender, ethnicity, occupation, religion, lifestyle, education level, number of household dogs, bovine and sheep, and density of dog feces in the courtyard. The major risk factors of human cystic echinococcosis were identified using a logistic regression model. RESULTS: Univariate logistic regression analysis showed 7 risk factors with statistical significance between the case and control groups, and age, lifestyle, number of household bovine, number of household sheep, number of house-hold dogs, and the density of dog feces in the courtyard were included in the multivariate logistic regression model (OR = 1.026, 4.792, 1.067, 1.022, 1.709 and 1.095, respectively). CONCLUSIONS: High age, pastoral nomadic lifestyle, high number of house-hold bovine, high number of household sheep, high number of household dogs and high density of dog feces in the courtyard are strongly associated with the riks of human cystic echinococcosis in Shiqu County.

Immunological methods for the diagnosis of oral mucosal diseases.

Immunological methods, which have been widely used in autoimmune blistering diseases (AIBDs) of the oral mucosa, can also be adopted as auxiliary diagnostic tools in oral lichen planus (OLP) and discoid lupus erythematosus (DLE). AIBDs, characterized by autoantibodies against structural proteins of keratinocytes or the basement membrane zone, clinically present as blisters and erosions of the oral mucosa. When atypical lesions occur, OLP or DLE may be confused with AIBDs. The improvement of diagnostic accuracy is necessary due to the significant differences in treatment and prognosis among these diseases. A variety of immunological methods are used for qualitative and quantitative detection of target antigens and autoantibodies. These methods can evaluate efficacy of treatment, monitor diseases and guide treatment decisions. In this review, we discuss the application of immunofluorescence, biochemical tests, and protein microarrays for AIBDs, OLP and DLE, as well as the differential diagnostic methods using immunological tests.

ACY 1215, a histone deacetylase 6 inhibitor, inhibits cancer cell growth in melanoma.

Histone deacetylase 6 (HDAC6) plays critical roles in dozens of malignant cancers, including melanoma. Therefore, inhibition of HDAC6 can be a potential strategy of targeting melanoma. ACY 1215 (ricolinostat), a selective HDAC6 inhibitor, is currently being clinically trialed in multiple cancers but not in melanoma. In this study, we tested the pre-clinical efficacy of ACY 1215 in melanoma cell lines. First, we found higher HDAC6 expression in melanoma cell lines than in an epidermal melanocyte cell line. Then, we observed the dose- and time-dependent reduction of cell proliferation caused by ACY 1215 treatment. Proliferation inhibition by ACY 1215 was associated with accumulation of acetylated tubulin but did not affect histone H3K9 acetylation. In addition, ACY 1215 induced cell apoptosis and G0/G1 cell cycle arrest. Finally, we show that ACY 1215 reduced tumor burden and increased survival in an in vivo mouse cell line xenograft model. All of these pre-clinical data indicate that HDAC6 is a potential target in melanoma, and that targeting HDAC6 in melanoma using ACY 1215 may be translationally relevant.

Upregulation of serum miR-103 predicts unfavorable prognosis in patients with colorectal cancer.

OBJECTIVE: Circulating microRNAs (miRNAs) have been reported as biomarkers for the early detection of colorectal cancer (CRC). We aimed at evaluating the diagnostic and prognostic value of serum miR-103 in CRC patients. PATIENTS AND METHODS: Quantitative reverse-transcription PCR (qRT-PCR) was applied to measure the miR-103 levels in blood samples of 96 patients and 60 controls. RESULTS: Our results demonstrated that serum miR-103 was overexpressed in CRC subjects and the receiver operating characteristic (ROC) curve analysis showed that serum miR-103 could differentiate CRC cases from controls with relatively high accuracy. In addition, serum miR-103 level was more frequently detected in CRC patients with positive lymph node metastasis, distant metastasis and advanced tumor stage. Moreover, serum miR-103 levels in 23 postoperative blood samples were lower than paired preoperative plasma specimens, and serum miR-103 levels were re-elevated in seven patients at recurrence. Furthermore, serum miR-103 was significantly correlated with worse clinical factors, as well as poorer recurrence-free survival or overall survival. Finally, multivariate analysis confirmed that serum miR-103 was an independent prognostic marker for CRC. CONCLUSIONS: Taken together, serum miR-103 might be a promising biomarker for diagnosis and prognosis of CRC.

Identification of key genes involved in HER2-positive breast cancer.

OBJECTIVE: As an invasive cancer, breast cancer is the most common tumour in women and is with high mortality. To study the mechanisms of HER2-positive breast cancer, we analyzed microarray of GSE52194. MATERIALS AND METHODS: GSE52194 was downloaded from Gene Expression Omnibus including 5 HER2-positive breast cancer samples and 3 normal breast samples. Using cuffdiff software, differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DE-lncRNAs) were screened. Functions of the DEGs were analyzed by Gene Ontology (GO) and pathway enrichment analyses. Then, protein-protein interaction (PPI) network of the DEGs was constructed using Cytoscape and modules of the PPI network were screened by CFinder. Moreover, lncRNA-DEG pairs were screened. RESULTS: Total 209 lncRNA transcriptions were predicted, and 996 differentially expressed transcriptions were screened. Besides, FOS had interaction relationships with EGR1 and SOD2 separately in module E and F of the PPI network for the DEGs. Moreover, there were many lncRNA-DEG pairs (e.g. TCONS_00003876-EGR1, TCONS_00003876-FOS, lnc-HOXC4-3:1-FOS, lnc-HOXC4-3:1-BCL6B, lnc-TEAD4-1:1-FOS and lnc-TEAD4-1:1-BCL6B), meanwhile, co-expressed DEGs of TCONS_00003876, lnc-HOXC4-3:1 and lnc-TEAD4-1:1 were enriched in p53 signaling pathway, MAPK signaling pathway and cancer-related pathways, respectively. CONCLUSIONS: ANXA1, EGR1, BCL6, SOD2, FOS, TCONS_00003876, lnc-HOXC4-3:1 and lnc-TEAD4-1:1 might play a role in HER2-positive breast cancer.

Aspergillus fumigatus diffusates suppress polymorphonuclear neutrophil phagocytic functions and respiratory burst levels in hematopoietic stem cell transplantation patients.

Invasive aspergillosis (IA) is a severe infection that commonly occurs in immunocompromised patients after hematopoietic stem cell transplantation (HSCT). The present study explores the effect of Aspergillus fumigatus diffusates (AfDs) on phagocytic function and superoxide anion (O2(-)) burst levels in polymorphonuclear neutrophils (PMNs) from post-HSCT patients. A. fumigatus conidia with or without AfD were used to stimulate the PMN from healthy donor or HSCT patient for two hours. PMN morphology was visualized by scanning electron microscopy. The levels of respiratory burst O2(-) produced by the PMNs were determined by flow cytometry. PMN phagocytic rates and phagocytic indexes were observed and calculated using periodic acid-Schiff (PAS) staining under a light-field microscope. No difference was found between the PMN phagocytic rates, phagocytic indexes, or O2(-) respiratory burst levels in health donor PMNs following treatments of A. fumigatus conidia with or without AfD. However, significant inhibition of these indices was seen in the PMNs from HSCT patients following treatment of A. fumigatus conidia plus AfD, compared to that with conidium treatment alone (P < 0.05). Therefore, AfD significantly inhibited the phagocytic function of PMNs from HSCT patients, potentially through inhibition of intracellular respiratory burst levels during phagocytosis. This suggests that the reason underlying the greater susceptibility of HSCT patients to aspergillosis might be the existence of AfD in vivo during infection. Further research on the mechanisms by which AfD affects the phagocytic function of PMNs from HSCT patients is therefore of great significance for the prevention of IA.

A comparison of proximal femoral locking compression plates with dynamic hip screws in extracapsular femoral fractures.

INTRODUCTION: The potential value of proximal femoral locking compression plate (PFLCP) for extracapsular femoral fractures has been discussed in several case reports; however, clinical control studies are lacking. Therefore, we performed a case control study to assess: (1) If PFLCP offers better functional results and fewer complications than dynamic hip screws (DHS)? (2) Which kind of extracapsular femoral fractures would benefit from PFLCP fixation? HYPOTHESIS: The PFLCP fixation offers better functional results and fewer complications than the DHS for the treatment of extracapsular fractures. PATIENTS AND METHODS: A total of 83 patients with extracapsular femoral fractures were recruited. Forty-one patients underwent PFLCP fixation, and 42 patients underwent DHS fixation. Patient information, operative time, blood loss, functional level (as assessed by Sanders' traumatic hip rating scale), bone union, and implant complications were compared for the two treatment groups. RESULTS: Patients with stable intertrochanteric fractures who underwent PFLCP fixation demonstrated shorter bone union time than the DHS fixation group (3.3 ± 0.2 vs. 4.3 ± 0.1 month; P<0.0001); however, both groups had 100% bone union and good to excellent scores on Sanders' traumatic hip rating scale (P=1.000). Patients with unstable intertrochanteric fractures who underwent PFLCP fixation experienced greater blood loss (619.0 ± 23.9 vs. 474.1 ± 19.8 ml; P<0.0001), which was mainly due to the need for open reduction (64.3% vs. 12.5%; P=0.003), compared to the DHS fixation group. No differences were identified with respect to bony union, functional level, or complications. Patients with subtrochanteric fractures who underwent PFLCP fixation demonstrated significantly shorter operative times (82.1 ± 4.3 vs. 102.2 ± 2.2 minutes; P<0.0001), less blood loss (751.8 ± 25.4 vs. 987.6 ± 32.0 ml; P<0.0001), shorter bone union times (5.2 ± 0.4 vs. 8.8 ± 1.0 month; P=0.006), more good to excellent Sanders' traumatic hip rating scale scores (92.9% vs. 55.5%; P=0.009), and fewer complications (14.2% vs. 66.6%; P=0.005) than the DHS fixation group. CONCLUSION: PFLCP fixation offers better functional outcomes and fewer complications for subtrochanteric femoral fractures but not for intertrochanteric femoral fractures. LEVELS OF EVIDENCE: Case control study, level III.