[The study of smoking impact on autophagy in alveolar macrophages of human silicosis].

Objective: To investigate the effect of smoking on autophagy in alveolar macrophages (AMs) of silicosis patients. Methods: In December 2019, a random sampling method was used to select 42 male patients with silicosis (19 cases of stage II and 23 cases of stage III) who were treated with large volume whole lung lavage from August to December 2017 in the Beidaihe sanatorium. According to the different smoking index of the study subjects (smoking index=smoking cigarette consumptions per day×years of smoking) , we divided them into high (Smoking index>400) , medium (200≤smoking index≤400) , low (smoking index <200) and non-smoking group. The levels of autophagy related proteins LC3, Beclin1, p62 and apoptosis related protein Cleaved Caspase-3 were detected by Western blot. The effects of smoking on autophagy activity of AMs in silicosis were analyzed. Results: The ratio of autophagy related protein LC3 II/LC3 I, the expression of Beclin1, p62, and apoptosis related protein Cleaved Caspase-3 in the high smoking group were significantly higher than that of the middle, low smoking group and the non-smoking group (P<0.05) . Conclusion: Smoking can aggravate the dysfunction of autophagic degradation in silicosis patients' AMs, which may accelerate the progress of silicosis through increasing apoptosis in AMs.

Overexpression of p300 correlates with poor prognosis in patients with cutaneous squamous cell carcinoma.

BACKGROUND: It has been suggested that the p300 transcriptional coactivator participates in the regulation of a wide range of cell biological processes, and mutations in p300 have been identified in various cancers. OBJECTIVES: To investigate p300 expression in cutaneous squamous cell carcinoma (cSCC) tissues and its effect on the outcome of patients with cSCC. METHODS: Immunohistochemistry (IHC) was performed on a tissue microarray to investigate p300 expression levels in cSCC tissues. Receiver operating characteristic (ROC) curve analysis, Kaplan-Meier plots and a Cox proportional hazards regression model were used to analyse the data. RESULTS: Based on the ROC curves, we defined the cut-off score for high p300 expression as > 55% of tumour cells positively stained. High expression of p300 was observed in 86 of 165 (52·1%) of the cSCC samples and six of 30 (20%) of the adjacent normal skin tissue samples (P < 0·001). High expression of p300 was positively correlated with lymph node metastasis (P = 0·006) and advanced clinical stage (P < 0·001). In univariate survival analysis, high expression of p300 was correlated with poor patient outcomes in terms of recurrence-free survival (P = 0·006) and overall survival (P < 0·001). Moreover, p300 expression was evaluated as an independent prognostic factor in a multivariate analysis (P = 0·004). CONCLUSIONS: Our results indicate that high p300 expression is associated with aggressive features of cSCC and suggest that p300 expression, as examined by IHC, will be a promising biomarker for predicting clinical outcomes in patients with cSCC.

Unmet information needs and clinical characteristics in patients with precancerous oral lesions.

The purpose of this study was to investigate associated factors of the unmet information needs of patients with precancerous oral lesions. For this cross-sectional descriptive study, we recruited patients with precancerous oral lesions from the otolaryngology outpatient department of a single medical centre in central Taiwan. Patients were assessed using a set of structure questionnaires to measure patients' state anxiety levels, attitudes towards cancer prevention and need for information. Patients' anxiety and attitudes towards cancer prevention were evaluated based on unmet needs and associated factors were determined. Among the 106 subjects surveyed, the most prominent unmet information needs were about obtaining the test results as soon as possible. Patients with precancerous oral lesions who had high levels of state anxiety, long duration of time since quitting betel nut chewing and were without a history of oral cancer were more likely to have unmet information needs. A high level of anxiety about precancerous oral lesions was more prevalent among patients with unmet information needs than among those whose information needs were met. Health education and individual counselling should be provided to satisfy the information needs of this population.

Low/negative expression of DDX3 might predict poor prognosis in non-smoker patients with oral cancer.

OBJECTIVE: DDX3 has diverse biological functions in translation control, cell growth regulation, and tumor progression. Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide with a poor clinical prognosis. The impact of DDX3 expression in OSCC is seldom discussed. MATERIALS AND METHODS: Tumor tissues and adjacent normal tissues were obtained from 324 patients with OSCC. In this study, we used immunohistochemical staining methods to investigate the associations between DDX3 expression and the clinicopathological characteristics of OSCC. RESULTS: Low/negative DDX3 expression in tumor cells was significantly associated OSCC patient characteristics including male gender (P < 0.001), smoking (P < 0.001), alcohol consumption (P < 0.001), betel quid chewing (P = 0.002), poor relapse-free survival (P = 0.001), and poor overall survival (OS) (P = 0.001). Patients with low/negative DDX3 expression, and particularly non-smoker OSCC patients, had significantly worse OS as defined by the log-rank test (P = 0.020 for all cases; P = 0.008 for non-smoker patients). In non-smoker patients with OSCC, low/negative DDX3 expression in tumor cells was associated with poor prognosis (P = 0.024) and a 3.802-fold higher death risk, as determined by Cox regression. CONCLUSIONS: Low/negative DDX3 expression in tumor cells was significantly associated with aggressive clinical manifestations and might be an independent survival predictor, particularly in non-smoker patients with OSCC.

Prediction of lymph node metastasis in T1/T2 tongue squamous cell carcinoma.

OBJECTIVES: In T1, T2, and clinically NO squamous cell carcinoma of the tongue, there is no reliable predictive variable to determine whether or not neck dissection is needed. Thus, we established a predictive score model based on tumour depth and other pathological variables. METHODS: We retrospectively reviewed 115 patients with T1 and T2 stage squamous cell carcinoma of the tongue. Their pathological variables were used to construct a score model for predicting the risk of cervical lymph node metastasis. RESULTS: A predictive score model was proposed using multivariate logistic regression analysis: Score = (2.694 x tumour depth (cm)) + (1.814 x lymphovascular invasion (yes = 1, no = 0)) + (1.175 x perineural invasion (yes = 1, no = 0)). The cutoff point was set at 2.7427. This predictive score model has a sensitivity of 91.2% and specificity of 65.4%. CONCLUSION: A predictive score model was built and a two-stage surgical approach was suggested for T1 and T2 squamous cell carcinoma of the tongue.

The predictive value of semaphorins 3 expression in biopsies for biochemical recurrence of patients with low- and intermediate-risk prostate cancer.

The class-3 semaphorins (Sema3A-F, Sema3s) are initially identified to play an important role in axonal guidance and cell migration. Our previous studies showed that Sema3s are also involved in the lymph node metastasis of prostate cancer, and are likely to modulate the behavior of prostate cancer with a pro-tumoral or an anti-tumoral effect, depending on their subtypes. However, no study has critically investigated the value of Sema3s expression in preoperative biopsy samples for the prediction of biochemical recurrence (BCR) after radical prostatectomy. In this study, we evaluated Sema3s expression by immunohistochemistry on 198 prostate biopsies with low- and intermediate-risk localized prostate cancer. The median follow-up was 42 months (range, 6-60) for all patients. Our results showed that Sema3A (OR: 0.19, P<0.001), Sema3B (OR: 0.38, P=0.003), Sema3E (OR: 0.39, P=0.007), and Sema3C (OR: 2.31, P=0.014) staining were independent predictors of BCR on multivariable analysis. Sema3A, 3B, 3C and 3E expression demonstrated potential values in predicting BCR upon survival analysis (P=0.001, P=0.003, P=0.029, P=0.037, respectively, Log-rank test). Our findings suggested that Sema3A, 3B, 3C, and 3E immunostaining in prostate biopsies, as supplements to clinicopathological parameters, could be used for predicting BCR in low- and intermediate-risk prostate cancer patients after radical prostatectomy. Specially, concurrent Sema3C-positive and Sema3A-negative, 3B-negative, 3E-negative staining is associated with an adverse prognosis. Further prospective studies in larger patient populations are needed to validate the current observations.

Left endobronchial intubation with a double-lumen tube using direct laryngoscopy or the Trachway® video stylet.

We compared direct laryngoscopy with a Macintosh blade vs indirect bronchoscopy with a Trachway® stylet, for endobronchial intubation with a left-sided double-lumen tube. We allocated participants scheduled for thoracic surgery and who had normal predicted laryngoscopy, 30 to each group. The mean (SD) intubation times with laryngoscope and Trachway were 48 (11) s vs 28 (4) s, respectively, p < 0.001. The rates of hoarseness on the first postoperative day, categorised as none/mild/moderate/severe, were 10/12/7/1 and 22/6/2/0, respectively, p = 0.008, without differences on subsequent days. Left endobronchial intubation with a double-lumen tube is slower using direct laryngoscopy and causes more hoarseness than indirect bronchoscopy with a Trachway stylet.

Transnasal endoscopic resection of vidian nerve schwannoma accompanied by sphenoid mucopyocele and oculomotor palsy: a case report.

Schwannomas are rare tumours arising from the peripheral nerve sheath. Nearly half of all schwannomas occur in the head and neck region, but the sinonasal tract is rarely involved. We report on an extremely rare case of vidian nerve schwannoma accompanied by mucopyocele with symptoms of oculomotor palsy and CSF leakage. An exclusively endoscopic endonasal approach was performed to excise the tumour and the dural defect was repaired. To our knowledge, this is the first time a vidian nerve schwannoma has been excised in an exclusively endoscopic approach. We first review the literature and then discuss the benefits for patients undergoing this type of operation.

Lower ataxia telangiectasia mutated (ATM) mRNA expression is correlated with poor outcome of laryngeal and pharyngeal cancer patients.

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase is a critical regulator in initiating DNA damage response and activating DNA repair. However, the correlation between ATM expression and the outcome of laryngopharyngeal cancer patients is unknown. We hypothesize that ATM expression is correlated with a worse outcome in laryngopharyngeal cancer patients. PATIENTS AND METHODS: The ATM messenger RNA (mRNA) expression of 80 tumors of laryngeal and pharyngeal cancer was examined by real-time quantitative RT-PCR. Overall survival rates were measured using Kaplan-Meier estimates and the log-rank tests. The adjusted hazard rate ratios (HRRs) were computed by multivariate Cox regressions. RESULTS: Reduced ATM mRNA was found in 65 of 80 studied cases. Lower ATM expression [tumor/normal <0.3, HRR = 2.49; 95% confidence interval (CI) 1.27-4.88], younger age (<55 years, HRR = 2.71; 95% CI 1.16-6.32), and larger tumor (T(3)/T(4), HRR = 2.21; 95% CI 1.10-4.44) were independent risk factors for survival. Patients with lower ATM and younger age (HRR = 6.51; 95% CI 2.05-20.66) or with lower ATM and T(3)/T(4) tumor (HRR = 5.23; 95% CI 2.04-13.40) exhibited the poorest outcome. CONCLUSION: The expression of ATM mRNA, which is frequently downregulated in laryngeal and pharyngeal cancers, could be a valuable prognostic marker.

Metallothionein-1 genotypes in the risk of oral squamous cell carcinoma.

BACKGROUND: We conducted an independent analysis of metallothionein 1 (MT-1) rs8052394, rs11076161, rs8052334, rs964372, rs7191779, and rs708274 in 587 individuals who were either healthy controls or subjects with oral squamous cell carcinoma (OSCC). METHODS: All participants provided a nucleic acid sample (blood) as well as epidemiologic information on covariates or "risk factors" for OSCC, including tobacco, alcohol, and areca quid use. The genotyping result was used in a logistic regression model that examined main effects as well as statistical interactions while controlling for confounders. RESULTS: MT-1 is involved in regulation of zinc and copper homeostasis. It also is a potent antioxidant and its polymorphisms correlate with the risk for OSCC. Rs11076161 A, rs964372 C, and rs7191779 C alleles were protective against OSCC (adjusted OR = 0.53, 0.49, 0.36, respectively; p < 0.05), whereas rs8052394 A alleles were associated with increased risk. Areca quid chewing and tobacco use were strong risk factors for developing the disease and were associated with 20- and 8-fold increases in adjusted risk (p < 0.05), respectively. CONCLUSIONS: Controlling for the effects of age, gender, areca quid, tobacco, and alcohol use, individuals with inherited the MT-1 rs11076161 AA, rs964372 CC, and rs7191779 GC genotypes may experience significant protection against OSCC, whereas individuals carrying the MT-1 rs8052394 A allele seem exposed to higher risk.

Endoscope-assisted transoral excision of a huge parapharyngeal pleomorphic adenoma.

The treatment of choice for a parapharyngeal pleomorphic adenoma is total surgical resection. We describe an endoscope-assisted transoral excision of a huge parapharyngeal pleomorphic adenoma, and discuss the benefits of this type of operation.

A pre-paid newborn hearing screening programme: a community-based study.

OBJECTIVES: To help obstetric hospitals and clinics to implement newborn hearing screening and to test the feasibility of a pre-paid model for screening. PATIENTS AND METHODS: From July 2005 to August 2008, we organised a coordinated newborn hearing screening team with portable automated auditory brainstem response (AABR) to provide in-patient screening after delivery and out-patient re-screening at one month of age in birthing facilities throughout Changhua County, Taiwan. This was a community-based study organised by otolaryngologists at a tertiary referral centre. RESULTS: Ten medical facilities participated in our screening programme. 7,139 out of 12,901 neonates delivered in these facilities during the period were screened for hearing loss. 105 (1.47%) babies who did not pass the in-patient screening were re-screened at one month old. Forty (0.56%) babies referred from the re-screening were sent for diagnostic work-up and six of them failed to show up. The overall follow-up rate was 94.3% (99/105). Eleven babies with bilateral hearing loss and eight babies with unilateral hearing loss were diagnosed. The incidence of bilateral hearing loss in our programme was 1.5/1000. The screening rate descended from medical centre to clinic (p < 0.0001). There was no significant difference between the referral rates for different levels of birthing facilities (p = 0.5611). CONCLUSIONS: Our study demonstrates that a pre-paid model using AABR is feasible at all three levels of medical facilities. Pre-paid community-based screening might be an option for developing countries in the implementation of universal newborn hearing screening.

Lethal sphenoid fungal sinusitis in an immunocompromised elderly patient.

Sphenoid fungal balls are rare and typically indolent lesions, unless superinfected by bacteria or invasive to adjacent neurovascular structures. If the identification or treatment of underlying complications is delayed in an immunocompromised patient, a catastrophic outcome may result. We report the case of an elderly female patient with poorly controlled diabetes mellitus suffering from sphenoid fungal sinusitis that is complicated by cavernous sinus thrombophlebitis and carotid artery stenosis. In spite of reasonable diagnosis and therapy, the patient's general condition deteriorated and she eventually died. The clinical presentation, diagnosis, and treatment strategy are discussed.

Is planned surgery important in sinonasal inverted papilloma?

OBJECTIVE: To evaluate which clinical characteristics of inverted papilloma (IP) can result easily in misdiagnosis by clinicians and to determine the recurrence rate of inverted papilloma depending on diagnosis confirmation pre-operatively, intra-operatively or post-operatively. PATIENTS AND METHODS: Fifty-one patients were treated for IP and 47 patients attended regular post-operative follow-up appointments for at least one year (mean: 54 months). RESULTS: The patients were assigned to 3 groups: group Ia, in which IP was not confirmed until the post-operative pathology findings; group Ib, in which IP was confirmed during the operation; and group II, in which IP was confirmed before the operation. There were nineteen (37%) patients in group Ia, nine patients (18%) in group Ib and twenty-three patients (45%) in group II. The recurrence rates for groups Ia, Ib and II were 33%, 11% and 5% respectively. CONCLUSIONS: The initial presentation of bilateral sinonasal disease can easily lead the doctor into the misdiagnosis of IP. Bony erosion, remodelling, and a widening of the natural orifice of the sinuses on a CT scan are useful signs indicating IP. The correct diagnosis prior to surgery is a determinant of outcome. The use of frozen sections should, however, improve outcome as well. In this study we highlight the high prevalence and relatively low control rate of misdiagnosed IP (pathology undetermined pre-operatively) and hope to remind clinicians that early recognition of the tumour is most beneficial to patients.

microRNA-144-3p suppresses human neuroblastoma cell proliferation by targeting HOXA7.

OBJECTIVE: Dysregulation of microRNAs (miRNAs) expression often resulted in abnormal cell behaviors. It has been demonstrated that miRs may serve as oncogenic or tumor suppressive functions in tumor. We investigated whether or not miR-144-3p has a role in the progression of human neuroblastoma (NB). PATIENTS AND METHODS: 46 NB patients were enrolled in this study. miR-144-3p expression in NB tissues and cell lines was detected by reverse transcription-quantitative polymerase chain reaction. The biological functions of miR-144-3p in NB were detected by cell counting kit-8 assay, flow cytometry assay, and wound-healing assay. Luciferase activity assay and Western blot assay were performed to validate the direct targets of miR-144-3p. RESULTS: We found miR-144-3p expression was reduced in NB tissues and cell lines and resulted in the stimulation of cell proliferation, cell cycle progression, and cell migration in vitro. Furthermore, we validated homeobox protein A7 (HOXA7) as a direct target of miR-144-3p. CONCLUSIONS: Taken together, these results demonstrated the tumor suppressive role of miR-144-3p in NB and may advance the understanding of the underlying mechanisms of miR-144-3p and HOXA7 in NB.

Bone mineral density as a dose-response predictor for osteoporosis: a propensity score analysis of longitudinal incident study (KCIS no. 39).

BACKGROUND: Osteoporosis is a global disease burden for aging society. The role of quantitative ultrasound (QUS) in the prediction for osteoporosis in a dose-response manner is hardly addressed. AIM: We aimed to show the dose-response of QUS measurement in the prediction for osteoporosis by a community-based study. DESIGN: A prospective cohort study. METHODS: Participants were recruited between 2000 and 2004. Demographic data and heel QUS measurement were collected at baseline. Diagnosis of osteoporosis was ascertained by the follow-up of this cohort over time. In order to reduce the imbalance of baseline characteristics in the observational study, we applied propensity score by using proportional odds regression analysis to match the quintiles of QUS T-score. RESULTS: A total of 44 957 subjects composed of 17 678 men (39.3%) and 27 279 women (69.7%) were recruited. After adjustments for propensity score, an increase in one unit of QUB T-score led to 7% reduction in the risk for osteoporosis [adjusted odds ratio (OR) = 0.93, 95% confidence interval (CI): 0.89-0.96, P < 0.0001]. Higher quintile of QUS T-score yielded a lower risk of osteoporosis with a gradient relationship [OR: 0.82 (95%CI: 0.72-0.92); OR: 0.81 (95%CI: 0.71-0.91); OR: 0.77 (95%CI: 0.68-0.87) and OR: 0.76 (95%CI: 0.67-0.86)] from the second to highest quintile opposed to first quintile (P < 0.0001). The cumulative incidence of osteoporosis was higher in the lower quintile during follow-up (log-rank test, P < 0.001). CONCLUSION: QUS is an independent predictor for osteoporosis in a dose-response manner using a large population-based cohort. Due to the lower cost and portability of QUS measurement, the pre-screening for osteoporosis by QUS can be considered in the area with limited resources can be a feasible and alternative method.

Expressions of miR-525-3p and its target gene SEMG1 in the spermatozoa of patients with asthenozoospermia.

BACKGROUND: Semenogelin 1 (SEMG1) is an important secretory protein in spermatozoa involved in the formation of a gel matrix encasing ejaculated spermatozoa. Previous studies show that the SEMG1 gene is highly expressed in spermatozoa from patients with asthenozoospermia (AZS); however, the underlying molecular mechanisms are not yet clear. OBJECTIVES: To study the molecular mechanism of high expression of SEMG1 gene and its potential roles in AZS. MATERIALS AND METHODS: Western blot and real-time PCR were used to detect the expression levels of SEMG1 protein and mRNA in the ejaculated spermatozoa from normozoospermic males and AZS patients. Bioinformatics analysis was used to predict miRNAs targeting for SEMG1 3'-untranslated region detection of the expression levels of all the candidate miRNAs in ejaculatory spermatozoa in AZS patients or normozoospermic volunteers. Luciferase reporter assays were performed to confirm it can directly bind to SEMG1. Correlation of miR-525-3p and SEMG1 mRNA expression with clinical sperm parameters were also analyzed. Finally, we conducted a follow-up study of reproductive history about all the subjects. RESULTS: SEMG1 mRNA and protein level were significantly higher in AZS patients compared to that in normozoospermic volunteers (p < 0.001). Subsequently, microRNA-525-3p (miR-525-3p) which was predicted as a candidate regulator of SEMG1 was found lower expressed in ejaculatory spermatozoa in AZS patients (p = 0.0074). Luciferase experiment revealed that microRNA-525-3p could directly target SEMG1 3'-untranslated region and suppress its expression. Importantly, our retrospective follow-up study showed that both low miR-525-3p expression and high SEMG1 expression level was significantly associated with low progressive sperm motility, abnormal sperm morphology, and infertility. DISCUSSION AND CONCLUSION: The elevated expression of SEMG1 and reduced expression of miR-525-3p are associated with AZS and male infertility. Our study provides a potential therapeutic target for the treatment of male infertility or for male contraception.