Pyridine-catalyzed ring-opening reaction of cyclopropenone with bromomethyl carbonyl compounds toward furan-2(5H)-ones.

We developed a pyridine-catalyzed annulation of diaryl cyclopropenone with bromomethyl carbonyl compounds leading to 5-carbonyl furan-2(5H)-ones. Pyridinium, derived from the reaction of bromomethyl carbonyl and pyridine, triggered the reaction by the inter-molecular Michael addition to cyclopropenone. This procedure was sensitive neither to air nor moisture and proceeded at room temperature with broad substrate scopes and good functional group tolerance in moderate-to-good yields. As such, it represents a facile and practical pathway leading to 5-carbonyl furan-2(5H)-one derivatives.

Cyclic increase in the ADAMTS1-L1CAM-EGFR axis promotes the EMT and cervical lymph node metastasis of oral squamous cell carcinoma.

The matrix metalloprotease A disintegrin and metalloprotease with thrombospondin motifs 1 (ADAMTS1) was reported to be involved in tumor progression in several cancer types, but its contributions appear discrepant. At present, the role of ADAMTS1 in oral squamous cell carcinoma (SCC; OSCC) remains unclear. Herein, The Cancer Genome Atlas (TCGA) database showed that ADAMTS1 transcripts were downregulated in head and neck SCC (HNSCC) tissues compared to normal tissues, but ADAMTS1 levels were correlated with poorer prognoses of HNSCC patients. In vitro, we observed that ADAMTS1 expression levels were correlated with the invasive abilities of four OSCC cell lines, HSC-3, SCC9, HSC-3M, and SAS. Knockdown of ADAMTS1 in OSCC cells led to a decrease and its overexpression led to an increase in cell-invasive abilities in vitro as well as tumor growth and lymph node (LN) metastasis in OSCC xenografts. Mechanistic investigations showed that the cyclic increase in ADAMTS1-L1 cell adhesion molecule (L1CAM) axis-mediated epidermal growth factor receptor (EGFR) activation led to exacerbation of the invasive abilities of OSCC cells via inducing epithelial-mesenchymal transition (EMT) progression. Clinical analyses revealed that ADAMTS1, L1CAM, and EGFR levels were all correlated with worse prognoses of HNSCC patients, and patients with ADAMTS1high/L1CAMhigh or EGFRhigh tumors had the shortest overall and disease-specific survival times. As to therapeutic aspects, we discovered that an edible plant-derived flavonoid, apigenin (API), drastically inhibited expression of the ADAMTS1-L1CAM-EGFR axis and reduced the ADAMTS1-triggered invasion and LN metastasis of OSCC cells in vitro and in vivo. Most importantly, API treatment significantly prolonged survival rates of xenograft mice with OSCC. In summary, ADAMTS1 may be a useful biomarker for predicting OSCC progression, and API potentially retarded OSCC progression by targeting the ADAMTS1-L1CAM-EGFR signaling pathway.

Versatile potassium vanadium fluorophosphate (KVPO4F) composites as Dual-Function cathode and anode materials for Potassium-Ion hybrid capacitors.

Potassium-based energy storage has emerged as a promising alternative for advanced energy storage systems, driven by the abundance of potassium, fast ion migration, and low standard electrode potential. Hybrid capacitors, which combine the desirable characteristics of batteries and supercapacitors, offer a compelling solution for efficient energy storage. In this study, we present the development of versatile composite materials, specifically potassium vanadium fluorophosphate (KVPO4F) composites, utilizing a sol-gel method. These composites enable tunable potassium storage and charge transport kinetics within regulated voltage windows, serving as both cathode and anode materials. The anode composite, composed of KVPO4F and hierarchical porous carbon (HPC), exhibited exceptional stability over 400 cycles within a low-voltage window. On the other hand, the cathode composite, consisting of battery-like KVPO4F and physisorption activated carbon (AC), demonstrated great potential as a cathode material, striking a balance between specific energy and cycle life within a regulated high-voltage window. By integrating KVPO4F/C as the anode and KVPO4F/AC as the cathode, we successfully created potassium-ion hybrid capacitors (PIHCs) that showcased an impressive capacity retention of 83% after 10,000 cycles within a high voltage window of 0.5-4.3 V. Furthermore, to explore the application of these materials in miniaturized energy storage, we fabricated potassium-ion micro hybrid capacitors (PIMHCs) with interdigitated electrodes. These devices exhibited a high areal energy density of 18.8 µWh cm-2 at a power density of 111.6 µW cm-2, indicating their potential for compact energy storage systems. The results of this study demonstrate the versatility and efficacy of the developed KVPO4F composite materials, highlighting their potential for future advancements in potassium-based energy storage technologies.

Microwave-regulated Bi nanoparticles on carbon nanotube networks as a freestanding electrode for flexible sodium-ion capacitors.

High capacity, long cycle life, and fast kinetics are highly desired for alloying anodes in sodium ion capacitors (SICs). However, the huge repeatedly volume changes during the alloying/dealloying process cause electrode pulverization, seriously degrading the capacity and cycling stability. To address this issue, we developed a microwave irradiation technology for the in-situ growth of nano-sized Bi uniformly anchored on the surface of carbon nanotubes (CNTs). The as-synthesized freestanding electrode film effectively retards the pulverization of Bi nanoparticles, enabling fast sodium storage kinetics for high-power performance (278.1 mAh g-1 @ 30 A g-1), as well as high-capacity retention of 94% for over 3,500 cycles. The coin-cell type SICs of a Bi/CNTs anode paired with an activated carbon (AC)/CNTs cathode can deliver a maximum energy density of 128.5 Wh kg-1 and a high power density of 12.3 kW kg-1 with a remaining energy density of 85 Wh kg-1. Additionally, the flexible quasi-solid SICs using a gel electrolyte demonstrated a high volumetric energy density of 21 mWh cm-3 with good cycling stability (90%) for over 1500 cycles. These results show great promise for our developed SICs as the next-generation energy storage to bridge the performance gap between batteries and supercapacitors, as well as for flexible energy storage applications.

[The role and mechanism of autophagy in lipopolysaccharide-induced inflammatory response of A549 cells]. / 自噬在脂多糖诱导的A549ç»†èƒžç‚Žç—‡ååº”ä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To study the role and mechanism of autophagy in lipopolysaccharide (LPS)-induced inflammatory response of human alveolar epithelial A549 cells. METHODS: A549 cells were stimulated with LPS to establish a cell model of inflammatory response, and were then grouped (n=3 each) by concentration (0, 1, 5, and 10 µg/mL) and time (0, 4, 8, 12, and 24 hours). The A549 cells were treated with autophagy inhibitor 3-methyladenine (3-MA) to be divided into four groups (n=3 each): control, LPS, 3-MA, and 3-MA+LPS. The A549 cells were treated with autophagy agonist rapamycin (RAPA) to be divided into four groups (n=3 each): control, LPS, RAPA, and RAPA+LPS. The A549 cells were transfected with the Toll-like receptor 4 (TLR4) overexpression plasmid to be divided into four groups (n=3 each): TLR4 overexpression control, TLR4 overexpression, TLR4 overexpression control+LPS, and TLR4 overexpression+LPS. The A549 cells were transfected with TLR4 siRNA to be divided into four groups (n=3 each): TLR4 silencing control,TLR4 silencing, TLR4 silencing control+LPS, and TLR4 silencing+LPS. CCK-8 assay was used to measure cell viability. Western blot was used to measure the protein expression levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4. RESULTS: After stimulation with 1 µg/mL LPS for 12 hours, the levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4 increased and reached the peak (P<0.05). Compared with the LPS group, the 3-MA+LPS group had reduced expression of autophagy-related proteins and increased expression of inflammation-related proteins and TLR4, while the RAPA+LPS group had increased expression of autophagy-related proteins and reduced inflammation-related proteins and TLR4 (P<0.05). The TLR4 overexpression+LPS group had reduced autophagy-related proteins and increased inflammation-related proteins compared with the TLR4 overexpression control+LPS group, and the TLR4 silencing+LPS group had increased autophagy-related proteins and reduced inflammation-related proteins compared with the TLR4 silencing control+LPS group (P<0.05). CONCLUSIONS: In the LPS-induced inflammatory response of human alveolar epithelial A549 cells, autophagic flux has a certain protective effect on A549 cells. TLR4-mediated autophagic flux negatively regulates the LPS-induced inflammatory response of A549 cells.

Impact of induction chemotherapy with concurrent chemoradiotherapy on nasopharyngeal carcinoma: A meta-analysis of randomized controlled trials.

Purpose: Induction chemotherapy followed by concurrent chemoradiotherapy (IC-CCRT) may be beneficial for nasopharyngeal carcinoma. However, the evidence on medium- and long-term effects of IC-CCRT is limited, and new randomized controlled trials (RCTs) have been published after 2018. Therefore, this systematic review and meta-analysis compared survival rates between patients with nasopharyngeal carcinoma receiving IC-CCRT or concurrent chemoradiotherapy (CCRT). Methods: Four databases were searched for RCTs on this topic. Two authors independently selected studies, assessed evidence, and extracted data on progression-free survival, overall survival, metastasis-free survival, and local recurrence-free survival. Available data were pooled in a random-effects model and mainly presented in hazard ratio (HR). Heterogeneity and small study effects were also evaluated. Results: Eleven RCTs (n = 3345) were deemed eligible. Pooled results revealed that patients receiving IC-CCRT had significantly improved progression-free survival (HR = 0.66, P < 0.05), overall survival (HR = 0.64, P < 0.05), metastasis-free survival (HR = 0.58, P < 0.05), and local recurrence-free survival (HR = 0.69, P < 0.05) at 3 years, but no significant difference in 5-year overall survival was noted between IC-CCRT and CCRT (HR = 0.84, P > 0.05). Most findings had low heterogeneity. Conclusion: IC-CCRT may benefit patients with nasopharyngeal carcinoma in the medium term, although no significant difference was observed in 5-year survival compared with CCRT. All outcomes had decreased survival rate from the 3-years to 5-year follow-up. Differences in patient ethnicities and regimens of IC-CCRT may be sources of heterogeneity.

Combined impacts of histamine receptor H1 gene polymorphisms and an environmental carcinogen on the susceptibility to and progression of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most frequently encountered type of oral cancer. Histamine receptor H1 (HRH1) was reported to play a crucial role in OSCC carcinogenesis, but impacts of genetic variants of HRH1 on OSCC remain unclear. Herein, we investigated the association between functional single-nucleotide polymorphisms (SNPs) of HRH1 and OSCC susceptibility or clinicopathologic variables by logistic regression models. HRH1 genotypes at four loci (rs346074, rs346076, rs901865, and rs2606731) were analyzed by a TaqMan allelic discrimination assay, and we found that patients harboring HRH1 rs901865 T and rs346074 T alleles had a significantly lower risk of developing larger tumor sizes (>T2) under a dominant model. Based on the environmental carcinogen exposure status, we observed that HRH1 rs901865 polymorphic variants were also associated with a lower risk of developing more-advanced clinical stages (III or IV) in patients with a betel-quid-chewing habit. Moreover, genotype screening of rs901865 and rs346074 in OSCC cell lines showed that cells respectively carrying the CT and TT genotypes expressed lower HRH1 levels compared to cells carrying the CC genotype of rs901865 and rs346074. Furthermore, analyses of TCGA and GEO databases revealed that HRH1 expression levels were upregulated in head and neck squamous cell carcinoma (HNSCC) and OSCC tissues compared to normal tissues and were correlated with larger tumor sizes and poorer prognoses. These results indicated the involvement of HRH1 SNPs rs901865 and rs346074 in OSCC development and support the interaction between HRH1 gene polymorphisms and an environmental carcinogen as a predisposing factor for OSCC progression.

Curcumin analog, GO-Y078, induces HO-1 transactivation-mediated apoptotic cell death of oral cancer cells by triggering MAPK pathways and AP-1 DNA-binding activity.

BACKGROUND: GO-Y078, a new synthetic analogue of curcumin (CUR), has higher oral bioavailability and anticancer activity than CUR, but the oncostatic effect of GO-Y078 on oral squamous cell carcinoma (OSCC) is largely unknown. RESEARCH DESIGN AND METHODS: In the present study, we examined the oncostatic properties and possible mechanisms of GO-Y078 on human SCC-9 and HSC-3 OSCC cells. RESULTS: Our results indicated that GO-Y078 showed a cytostatic effect against OSCC cells, and this antiproliferative phenomenon stemmed from a mechanism involving multiple levels of cooperation, including cell-cycle G2/M arrest and apoptosis induction. Mechanistically, GO-Y078 treatment induced caspase-mediated apoptosis via upregulating two apoptosis-modulating proteins, SMAC/DIABLO and heme oxygenase (HO)-1. GO-Y078 transcriptionally induced upregulation of the HO-1 gene by increasing the AP-1 DNA-binding activity, which was initiated by activation of the p38 /JNK1/2 pathways. In the clinic, patients with head and neck cancers expressed lower HO-1 and SMAC/DIABLO levels in primary cancer tissues compared to normal tissues. Clinical datasets also revealed that patients with head and neck cancers expressing high HO-1 had afavorable prognosis. CONCLUSIONS: Our results provide new insights into the role of GO-Y078-induced molecular regulation in suppressing OSCC growth and suggest that GO-Y078 has potential therapeutic applications for OSCC.

Fully Automatic Registration Methods for Chest X-Ray Images.

PURPOSE: Image registration is important in medical applications accomplished by improving healthcare technology in recent years. Various studies have been proposed in medical applications, including clinical track of events and updating the treatment plan for radiotherapy and surgery. This study presents a fully automatic registration system for chest X-ray images to generate fusion results for difference analysis. Using the accurate alignment of the proposed system, the fusion result indicates the differences in the thoracic area during the treatment process. METHODS: The proposed method consists of a data normalization method, a hybrid L-SVM model to detect lungs, ribs and clavicles for object recognition, a landmark matching algorithm, two-stage transformation approaches and a fusion method for difference analysis to highlight the differences in the thoracic area. In evaluation, a preliminary test was performed to compare three transformation models, with a full evaluation process to compare the proposed method with two existing elastic registration methods. RESULTS: The results show that the proposed method produces significantly better results than two benchmark methods (P-value ≤ 0.001). The proposed system achieves the lowest mean registration error distance (MRED) (8.99 mm, 23.55 pixel) and the lowest mean registration error ratio (MRER) w.r.t. the length of image diagonal (1.61%) compared to the two benchmark approaches with MRED (15.64 mm, 40.97 pixel) and (180.5 mm, 472.69 pixel) and MRER (2.81%) and (32.51%), respectively. CONCLUSIONS: The experimental results show that the proposed method is capable of accurately aligning the chest X-ray images acquired at different times, assisting doctors to trace individual health status, evaluate treatment effectiveness and monitor patient recovery progress for thoracic diseases.

Combined Impacts of Genetic Variants of Long Non-Coding RNA MALAT1 and the Environmental Carcinogen on the Susceptibility to and Progression of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity, and long non-coding (lnc)RNA of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was recently reported to play a crucial role in OSCC development and progression. However, potential effects of genetic variants of MALAT1 on the development of OSCC are still unclear. Herein, we performed a case-control study in 1350 patients with OSCC and 1199 healthy controls to evaluate the association between functional single-nucleotide polymorphisms (SNPs) of MALAT1 and OSCC susceptibility, as well as its clinicopathologic characteristics. A TaqMan allelic discrimination assay was used to genotype four tagging SNPs, viz., rs3200401 C>T, rs619586 A>G, rs1194338 C>A, and rs7927113 G>A, and results showed that the MALAT1 rs3200401 T allele had a lower risk of OSCC (adjusted odds ratio (AOR): 0.779, 95% confidence interval (CI): 0.632~0.960, p=0.019) and a higher risk of developing moderately (grade II)/poorly (grade III) differentiated OSCC (AOR: 1.508-fold, 95% CI: 1.049~2.169, p=0.027) under a dominant model. According to environmental carcinogen exposure, patients with a betel quid-chewing habit who carried the T allele of rs3200401 more easily developed high-grade (II/III) OSCC (AOR: 1.588, 95% CI: 1.055~2.390, p=0.027), and patients with the same genotype but who did not chew betel quid had a lower risk of developing lymph node metastasis (AOR: 0.437, 95% CI: 0.255~0.749, p=0.003). In addition to rs3200401, the rs619586 AG/GG genotype was associated with increased risks of developing advanced stages (III+IV) and larger tumor sizes (>T2) compared to the AA genotype, especially in the subgroup of betel quid chewers. Furthermore, analyses of clinical datasets revealed that the MALAT1 expression level was upregulated in OSCC compared to normal tissues, especially in the betel quid-chewing population. These results indicated involvement of MALAT1 SNPs rs3200401 and rs619586 in the development of OSCC and support the interaction between MALAT1 gene polymorphisms and the environmental carcinogen as a predisposing factor for OSCC progression.

A real-time camera-based adaptive breathing monitoring system.

Breathing is one of the vital signs used to assess the physical health of a subject. Non-contact-based measurements of both breathing rate and changes in breathing rate help monitor health condition of subjects more flexibly. In this paper, we present an improved real-time camera-based adaptive breathing monitoring system, which includes real time (1) adaptive breathing motion detection, (2) adaptive region of interest detection to eliminate environmental noise, (3) breathing and body movement classification, (4) respiration rate estimation, (5) monitor change in respiration rate to examine overall health of an individual, and (6) online adaptation to lighting. The proposed system does not pose any positional and postural constraint. For evaluation, 30 videos of 15 animals are tested with drugs to simulate various medical conditions and breathing patterns, and the results from the proposed system are compared with the outputs of an existing FDA-approved invasive medical system for patient monitoring. The results show that the proposed method performs significantly correlated RR results to the reference medical device with the correlation coefficient equal to 0.92 and p-value less than 0.001, and more importantly the proposed video-based method is demonstrated to produce alarms 10 to 20 s earlier than the benchmark medical device. Graphical abstract The proposed system flowchart to extract the respiratory pattern from video.

Office-based salivary gland ductal irrigation in patients with chronic sialoadenitis: A preliminary study.

BACKGROUND/PURPOSE: To evaluate the therapeutic responsiveness of office-based salivary gland ductal irrigation in patients with chronic sialoadenitis. METHODS: Between August 2017 and April 2019, 55 patients comprising the following three disease groups were enrolled: Sjogren's syndrome: 39 patients; postradiotherapy sialoadenitis: ten patients; and post-RAI sialoadenitis: six patients. Quantitative salivary scintigraphy was recorded, and a formulated questionnaire including the Summated Xerostomia Inventory was utilized to assess acute/chronic symptoms. All patients received at least three serial salivary gland ductal irrigations with a one-month interval in our outpatient department. RESULTS: The general response rates for each disease groups are as follows: Sjogren's syndrome: 61.5% (24/39); postradiotherapy: 60% (6/10); and post-RAI: 83.3% (5/6). Among the patients with Sjogren's syndrome, the parotid scintigraphic Tmin showed a significant positive correlation with the responsiveness of salivary irrigation (P = 0.046), whereas the treatment tended to be irresponsive in patients who previously took medicine for their related discomfort (P = 0.009). In the postradiotherapy and post-RAI groups, no significant factors were found to be associated with the responsiveness of irrigation. CONCLUSION: Simple salivary ductal irrigation without complex equipment can be performed as an outpatient procedure to alleviate glandular swelling or xerostomia in patients with Sjogren's syndrome, postradiotherapy sialoadenitis or post-RAI sialoadenitis, and it can be considered an alternative management approach for patients refractory to conventional strategies.

Development of a poly-L-lactide salivary duct stent.

Obstructive salivary gland diseases are common conditions that arise following the disruption of the secretary ductal system and usually results in the swelling and pain of the affected gland(s). There has been an increase in the use of sialendoscopy for the treatment and diagnosis of obstructive salivary gland infection. If damage occurs to a duct or papilla following sialendoscopy, a stent may be necessary to prevent restenosis and for maintaining the salivary duct open after complete sialendoscopy. Currently, there are only non-biodegradable salivary duct stents available. The aim of the current study was to establish a methodology for the fabrication of a biodegradable poly-L-lactide (PLLA) salivary duct stent and to examine its function in an animal model. In the current study, PLLA was used to fabricate a salivary duct stent, which was compared with other commercially available non-biodegradable products. The mechanical tests revealed that the tensile strength of the PLLA stent was similar to that of the commercially available non-biodegradable stents. The Young's modulus, which measures the stiffness of a solid material, was significantly higher for the PLLA stent compared with the commercially available non-biodegradable stents. In addition, the current study demonstrated that the PLLA salivary duct stent was easily used with current sialendoscopy techniques, allowing accurate stent placement in an animal model.

Cost-effectiveness analysis of endoscopic tympanoplasty versus microscopic tympanoplasty for chronic otitis media in Taiwan.

BACKGROUND: Health care systems and physicians need to conform to budgets and streamline resources to provide cost-effective quality care. Although endoscopic tympanoplasty (ET) has been performed for decades, no studies on the cost-effectiveness of ET and microscopic tympanoplasty (MT) for treating chronic otitis media have been published. The present study aimed to compare the cost-effectiveness of ET and MT for treating chronic otitis media. METHODS: This study was performed using a Cohort-style Markov decision-tree economic model with a 30-year time horizon. The economic perspective was that of a third-party payer (Taiwan National Health Insurance System). Two treatment strategies were compared, namely ET and MT. The primary outcome was the incremental cost per quality-adjusted life year (QALY). Probabilities were obtained from meta-analyses. Costs were obtained from the published literature and Taiwan National Health Insurance System database. Multiple sensitivity analyses were performed to account for data uncertainty. RESULTS: The reference case revealed that the total cost of ET was $NT 20,901 for 17.08 QALY per patient. By contrast, the total cost of MT was $NT 21,171 for 17.15 QALY per patient. The incremental cost effectiveness ratio for ET versus that of MT was $NT 3703 per QALY. The cost-effectiveness acceptability curve indicated that ET was comparable to MT at a willingness-to-pay threshold of larger than $NT 35,000 per QALY. CONCLUSION: This cost-effectiveness analysis indicates that ET is comparable to MT for treating chronic otitis media in Taiwan. This result provides the latest information for physicians, the government, and third-party payers to select proper clinical practice.

Short-term Subjective and Objective Outcomes of Patients Receiving Endoscopic Transcanal Myringoplasty for Repairing Tympanic Perforations.

Objective Endoscopic transcanal myringoplasty (ETM) has been an emerging technique for repairing tympanic perforations since the late 1990s. Objective outcomes (ie, graft success rates and hearing results) of patients who received ETM are well documented; however, subjective outcomes of these patients have rarely been reported. Hence, this study evaluated subjective and objective outcomes of patients who received ETM for repairing tympanic perforations. Study Design Prospective study. Setting Tertiary care university hospital. Patients and Methods Patients who underwent ETM for perforations of the tympanic membrane were included. We evaluated subjective variables of patients receiving ETM as the primary outcome and objective variables as the secondary outcome. Results In total, 91 ears that underwent ETM were included. The mean pain scale score was 0.1 (range, 0-2) on postoperative day 3. The mean duration of pain medication was 2.0 (range, 0-3) days. The mean number of days required to resume routine activities was 1.0 (range, 1-2) days. The overall graft success was determined postoperatively at 3 months in 80 of 91 ears (87.9%). Closure of the air-bone gap to within 20 dB was achieved in 79 (86.8%) ears. Conclusion In this study, patients who received ETM had mild postoperative pain and resumed routine activities early. These patients also exhibited favorable graft success rates and hearing results at 3 months postoperatively. On the basis of our results, we conclude that patients who receive ETM for the repair of tympanic perforations have favorable short-term subjective and objective outcomes.

Endoscopic transcanal myringoplasty for tympanic perforations: An outpatient minimally invasive procedure.

OBJECTIVE: Since the 1950s, microscopic myringoplasty has been the standard surgery for repairing a perforated tympanic membrane. In addition to conventional microscopic myringoplasty, endoscopic myringoplasty has been an emerging technique since the late 1990s. This study evaluated the efficacy of endoscopic transcanal myringoplasty for repairing tympanic perforations and examined the minimally invasive feature of this technique (no postauricular incision, no canalplasty). METHODS: We retrospectively reviewed the medical records of patients who underwent endoscopic transcanal myringoplasty for perforations of the tympanic membrane. The main outcome was the overall rate of graft success of endoscopic transcanal myringoplasty. RESULTS: A total of 181 patients were included in the analysis. The overall graft success was determined in 163 of 181 patients (92.8%). The mean preoperative and postoperative air-bone gaps were 19.3dB and 7.8dB, respectively, revealing a significant improvement of 11.5dB (Cohen's d, 1.27; 95% CI, 1.03-1.50; P<0.05; paired t test) in the air-bone gap. The rate of graft success with partial visualization of the perforation margin was comparable to that with complete visualization of the perforation margin. Larger sizes of perforations were significantly associated with lower rates of graft success (P<0.01). CONCLUSION: Our study revealed that the rate of graft success and hearing results of endoscopic transcanal myringoplasty and microscopic myringoplasty are comparable for repairing perforations of the tympanic membrane. Visualization of the perforation margin by otoscopy did not affect the rate of graft success. However, endoscopic transcanal myringoplasty is less invasive because this technique does not require postauricular incision, canalplasty, and general anesthesia.

Value and application of trimodality therapy or definitive concurrent chemoradiotherapy in thoracic esophageal squamous cell carcinoma.

BACKGROUND: Few large, prospective, randomized studies have investigated the value and optimal application of neoadjuvant chemoradiotherapy followed by surgery (trimodality therapy) or definitive concurrent chemoradiotherapy (CCRT) for patients with thoracic esophageal squamous cell carcinoma (TESCC). METHODS: The authors analyzed data from patients with TESCC in the Taiwan Cancer Registry database. To compare their outcomes, patients with TESCC were enrolled and categorized into the following groups according to treatment modality: group 1, those who underwent surgery alone; group 2, those who received trimodality therapy; and group 3, those who received definitive CCRT. Group 1 was used as the control arm for investigating the risk of mortality after treatment. RESULTS: In total, 3522 patients who had TESCC without distant metastasis were enrolled. Multivariate Cox regression analysis indicated that a Charlson comorbidity index score ≥3, American Joint Committee on Cancer stage ≥IIA, earlier year of diagnosis, alcohol consumption, cigarette smoking, and definitive CCRT were significant, independent predictors of a poor prognosis. After adjustment for confounders, adjusted hazard ratios and 95% confidence intervals (CIs) for overall mortality in patients with clinical stage I, IIA, IIB, IIIA, IIIB, and IIIC TESCC were 2.01 (95% CI, 0.44-6.18), 1.65 (95% CI, 0.99-2.70), 1.48 (95% CI, 0.91-2.42), 0.66 (95% CI, 1.08-1.14), 0.39 (95% CI, 0.26-0.57), and 0.44 (95% CI, 0.24-0.83), respectively, in group 2; and 2.06 (95% CI, 1.18-3.59), 2.65 (95% CI, 1.76-4.00), 2.25 (95% CI, 1.49-3.39), 1.34 (95% CI, 0.79-2.28), 0.82 (95% CI, 0.57-1.17), and 0.93 (95% CI, 0.51-1.71), respectively, in group 3. CONCLUSIONS: Trimodality therapy may be beneficial for the survival of patients with advanced-stage (IIIA-IIIC) TESCC, and CCRT might be an alternative to surgery alone in these patients. Cancer 2017;123:3904-15. © 2017 American Cancer Society.

Learning curve for endoscopic tympanoplasty: Initial experience of 221 procedures.

BACKGROUND: The learning curve for endoscopic tympanoplasty has never been quantitatively reported. The present study depicted the learning curve for endoscopic tympanoplasty and evaluated how many procedures an otologist requires to attain proficiency in this technique. METHODS: We reviewed the medical charts of consecutive patients who underwent endoscopic tympanoplasty between January 1, 2013 and June 1, 2015. We enrolled patients with simple perforations of the tympanic membrane and excluded those with ossicular chain disease. The main outcome was learning curves for endoscopic tympanoplasty, which illustrated changes in the mean operative time and graft success rate according to the patient numbers. We subsequently estimated and verified the threshold value using statistical methods. RESULTS: A total of 221 procedures were included. For the learning curve of the mean operative time, the time gradually decreased from 75 minutes to 55 minutes. After the 150th patient, the mean operative time stabilized to < 60 minutes. For the learning curve of the graft success rate, the rate sharply increased from 75% to 95%. After the 50th patient, the graft success rate reached a plateau and fluctuated between 85% and 100%. We subsequently verified that the 50th and 150th patients were appropriate threshold values. Moreover, the graft success rate of perforations < 50% was significantly higher than that of perforations > 50%. CONCLUSION: These curves illustrate significant progress of the surgeon during the first 50 patients, considering the graft success rate, reaching an advanced level after the 150th patient, considering the mean operating time.

Effect of probiotics on digestibility and immunity in infants: A study protocol for a randomized controlled trial.

The gastrointestinal (GI) tract of a fetus in utero is sterile but it becomes colonized with environmental microorganisms shortly after birth. Since the gut microbiota undergoes substantial changes in early life, healthy gut microflora is essential to an infant's gut health and immune system and probably also has an effect on overall health status in later life. Probiotics, defined as viable microbial preparations that have a beneficial effect on the health of the host, represent a rapidly expanding field. Although randomized controlled trials using probiotics in infants have shown promising results in the prevention and treatment of common diseases such as diarrhea and allergy, little is known about whether probiotics could offer benefits to healthy infants. We have designed a randomized controlled trial to test the hypothesis that an oral preparation of probiotics is superior to placebo in improving digestive and immune function in healthy infants.The trial will be a randomized, double-blind, placebo-controlled, 2-parallel-group study in Shanghai, China. After a 2-week run-in period, 200 exclusively formula-fed healthy infants aged 4 to 6 months will be randomly allocated to receive either a probiotic product containing Bifidobacterium infantis R0033, Bifidobacterium bifidum R0071, and Lactobacillus helveticus R0052 or an identical placebo once daily for 4 weeks and will be followed up for 8 weeks. The duration of the subject's participation will be 14 weeks, with a total of 5 visits: inclusion (Visit 1, Day 1), start of intervention (V2, D15), end of intervention (V3, D44), and follow-up (V4 and V5, D72 and D100). Stool and saliva samples will be collected at the first 3 visits to measure microbial populations and secretory immunoglobulin A (SIgA), respectively. Physical examination will be performed at each visit, and tolerance records will be completed 1 day prior to each visit. The primary endpoints will be the changes in the composition of fecal microbiota, particularly the Bifidobacterium bifidum population. The secondary endpoints will include the change in salivary SIgA level, growth parameters, digestive tolerance, and adverse events.An effective, practical, and acceptable probiotic intervention in manipulating the gut microbiota and boosting the immune system in formula-fed infants would represent a major clinical advance. The administration of probiotic supplementation or follow-on formula to infant may be associated with some clinic benefits.

Associations of maternal pre-pregnancy body mass index and gestational weight gain with birth outcomes in Shanghai, China.

Recent data suggests that abnormal maternal pre-pregnancy body mass index (BMI) or gestational weight gain (GWG) is associated with unfavorable delivery outcomes. However, limited clinical evidence is available to support this correlation in China. Participating 510 mother-infant pairs were recruited from the Shanghai First Maternity and Infant Hospital, China, between January 1st and 30th 2016. Maternal pre-pregnancy BMI was categorized according to the China's classification and GWG according to the 2009 Institute of Medicine recommendations (IOM). Linear regression tested the associations between pre-pregnancy BMI or GWG and length of gestation, birthweight, length, and head circumference. Logistic regression assessed the associations between pre-pregnancy BMI or GWG and macrosomic, small- (SGA) and large- (LGA) for-gestational-age infants. Overweight/obese women showed increased length of gestation and birthweight, but did not have a higher risk of macrosomic and LGA infants compared with normal weight women. Women with excessive GWG showed increased length of gestation, birthweight, length, and head circumference, and were more likely to deliver macrosomic and LGA infants compared with women with adequate GWG. Although a relatively low proportion of women from Shanghai area are overweight/obese or exhibit excessive GWG, both high pre-pregnancy BMI and excessive GWG influence perinatal outcomes.