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Background To observe the long-term survival and late adverse events in a phase Ⅰ/Ⅱ trial (NCT01843049) of dose escalation for thoracic esophageal squamous cell carcinoma (ESCC) with simultaneous integrated boost (SIB) technique. Methods Patients with ESCC were treated with escalating radiation dose of four predefined levels. Dose of 62.5–64 Gy/25–32 fractions was delivered to the gross tumor volume (GTV), with (Level 3&4) or without (Level 1&2) a SIB up to 70 Gy for pre-treatment 50% SUVmax area of GTV. Patients also received 2 cycles of chemotherapy of cisplatin and fluorouracil concurrently and 2 more cycles after radiotherapy. Results Median follow-up duration was 17.2 (2.5–83.4) months for all 44 patients and 47.2 (3.9–83.4) months for 25 survivors. The 3-year overall survival and progression-free survival rates were 57.6% and 41.0%, respectively. One, one, four and twelve severe (grade ≥ 3) esophageal late adverse events (SEAE) occurred in patients of Level 1/2/3/4 (n = 5/10/16/13), with median occurrence time of 6.5 months. In univariable and multivariable competing risk models, maximal dose of the esophagus (Dmax) was found to have significant impact on the incidence of SEAE, and the cutoff distinguishing patients who developed SEAE or not was 77 Gy. Conclusion Boosting the gross tumor to 63 Gy while delivering 50.4 Gy to subclinical diseases in 28 fractions in locally advanced ESCC is well tolerated with promising long-term survival. Intenser dose regimen should be considered with caution before further toxicity assessment. Esophageal Dmax was significantly associated with severe late esophageal injury, while more findings of dose-volume predictors need larger-sample investigation.

Objective: Few studies have identified a relationship between cognitive deficits and altered event-related potentials (ERPs), which measure the synchronous activity of neurons in response to a stimulus in patients with generalized anxiety disorder (GAD). In this study, we intended to explore the relation between cognitive function and ERP in patients with GAD. Methods: Fourteen drug-free participants with GAD and 14 healthy controls were recruited. ERPs were measured, and neuropsychological tests were administered. We compared the differences of the data between two groups of the study participants. Results: Poor performances of full IQ and the numbers of the categories completed on the Wisconsin Card Sorting Test were found significantly correlated with increased frontal lobe latency in the patients with GAD (Spearman's ρ = −0.70, p < 0.05; Spearman's ρ = −0.85, p < 0.01), respectively, but not in the controls. Conclusion: As ERPs represent an index of information speed, we propose that patients with GAD could exhibit deficits in tasks requiring mental speed.

A case of the absorption of corona virus disease 2019 (COVID-19) promoted by professor Xu ZOU's acupuncture technique for "benefiting kidney and strengthening anti-pathogenic qi" is introduced. A female patient suffered from COVID-19, 64 years old, had been treated with acupuncture and Chinese herb granules for 10 days on the base of the oral administration of moxifloxacin. In the re-examination, the chest CT image indicated that the absorption of COVID-19 was obvious as compared with before, the nucleic acid test of novel corona virus was negative and the patient narrated no obvious discomfort. Acupuncture therapy plays its active adjuvant effect in the whole process of the treatment of COVID-19.

Abnormal autonomic nervous system (ANS) function may result in poor outcomes in patients with schizophrenia. Altered cardio-respiratory coupling, which indicates suppression of vagal activity, was identified as an important trait in patients with schizophrenia and their unaffected relatives. Heart rate variability (HRV) in standardized bedside reflex tests has been studied, mostly in medicated patients with schizophrenia whose ANS function could be influenced by medication. Our study aimed to explore the autonomic function differences between drug-naïve patients with schizophrenia and healthy individuals during challenge tests combining respiration and HRV analysis. Forty-two drug-naïve patients with schizophrenia were matched with 42 healthy controls in terms of age and gender. Their beat-to-beat blood pressure and heart rate were monitored in the supine position as a survey of ANS function, and the mean heart rate range (MHRR) was measured under deep-breathing challenge. A decreased MHRR, a sensitive sign indicating an impaired parasympathetic response, during the deep-breathing challenge among the drug-naïve patients with schizophrenia was found. Drug-naïve patients with schizophrenia may have a parasympathetic dysfunction in the early stages of schizophrenia before medication is introduced, which could be considered a neurobiological marker in the pathophysiology of schizophrenia.

BACKGROUND Facial cosmetic procedures become popular for people with a desire to have a younger appearance, and cosmetic technology has developed rapidly over the past several decades. However, increasing complications related to cosmetic injections have been reported, and infection is one of the most serious problems and can cause anxiety and facial injury. We here report a case of Majocchi's granuloma (MG) caused by Trichophyton rubrum after facial injection of hyaluronic acid. CASE SUMMARY A 37-year-old woman presented to our hospital with a history of red papules, nodules, and abscesses on her left zygomatic arch for 2 mo. She had received a cosmetic injection of hyaluronic acid on the left side of her face prior to the appearance of the lesions. MG caused by Trichophyton rubrum after facial injection of hyaluronic acid was diagnosed based on morphology and molecular biological identification. In vitro antifungal susceptibility testing was conducted according to the Clinical and Laboratory Standards Institute M38-A2 method. Minimal inhibitory concentrations were used to evaluate the antifungal susceptibility. The antifungal agents and their minimal inhibitory concentrations for the strain were terbinafine (< 0.5 μg/mL), itraconazole (0.06 μg/mL), amphotericin B (0.25 μg/mL), fluconazole (32 μg/mL), voriconazole (0.125 μg/mL), posaconazole (0.125 μg/mL), and isavuconazole (0.06 μg/mL). We initially administered 250 mg/d oral terbinafine for 2 mo, but the patient still had painful papules, nodules and abscesses on her face. Then, we adjusted the treatment to itraconazole 400 mg/d for 8 wk based on the in vitro antifungal susceptibility testing results. The skin lesions improved significantly, and there was no recurrence during follow-up. CONCLUSION This case revealed that facial injection of hyaluronic acid may cause serious MG. Antifungal susceptibility testing should be considered in the treatment of MG caused by Trichophyton rubrum.

Background To investigate the clinicopathologic characteristics and survival outcomes of patients with thymic epithelial tumors (TET) according to age at diagnosis. Results A total of 4431 patients were analyzed. Gender, race, tumor histology and surgery were similar between different age groups. The 0-18 group was associated with a higher risk of distant metastasis. Compared to patients aged above 80, the hazard ratios (HR) for patients aged 0-18, 19-30, 31-40, 41-50, 51-60, 61-70, 71-80 were 1.079, 0.739, 0.614, 0.621, 0.633, 0.673, 0.861, respectively. From the subgroup analysis for the adult patients who were above 19 years old, we found that the 19-70 group had significant better cancer specific survival (CSS) and overall survival (OS) than the above 70 group. Conclusions Age is a strong independent prognostic factor for survival in TET. Pediatric TET has a higher risk of distant metastasis and an inferior CSS. For the adults who were above 19, patients older than 70-year-old were associated with a shorter CSS. Methods Information of 4431 TET patients was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic features, clinicopathologic characteristics and survival outcomes were compared between patients diagnosed at different age groups (0-18, 19-30, 31-40, 41-50, 51-60, 61-70, 71-80, above 80).

BackgroundThere are no optimal regimens for advanced thymic epithelial tumors (TETs) when front-line chemotherapy fails. In this study, we aimed to assess the activity of Bevacizumab in combination with routine chemotherapeutic regimen.MethodsPatients with advanced TETs who had failed after previous chemotherapy were enrolled in this study. Paclitaxel (160mg/m2) or cisplatin (70mg/m2) and carboplatin (area under the curve, 6) plus Bevacizumab (7.5mg/kg) were intravenously injected on day 1.The treatment was repeated every 3 weeks until the disease progressed or intolerable toxicities occurred.ResultsBetween March 2018 and August 2020, a total of 49 patients (21 thymoma and 28 thymic carcinoma) received the new treatment. There were 28 men and 21 women with a median age of 50 years (range: 21-73 years).The median number of cycles was 3 (range: 1-6) per patient. The objective response rate (ORR) for all patients was 43% (21/49). The ORRs for thymoma and thymic carcinoma were 24% and 57%, respectively. The median progression free survival for thymoma and thymic carcinoma were 6 and 8 months, respectively. Hematological toxicities were the main side effects.ConclusionsPaclitaxel and platinum plus Bevacizumab showed promising effect in refractory or relapsed advanced TETs without severe toxicity. Even applied as salvage therapy, this regimen resulted in better ORR than the front-line chemotherapy.

Gingival enlargement (GE) is one of the most common soft tissue problems encountered during fixed orthodontic treatment. Aims: This study aimed to evaluate the factors affecting GE in adolescents and young adults, compared with their normal peers.This is a cross-sectional comparative study. The sample consisted of 329 subjects (ages 10-30 years) of both genders, which was divided into four main groups: The control group (G0) with no orthodontic treatment; subjects who underwent orthodontic treatment were divided according to treatment duration into G1 (4-12 months), G2 (13-24 months), and G3 (24 months). The clinical examinations included the level of debris, calculus (simplified oral hygiene), and GE indices. Regression analyses were used to assess the GE association in all the studied groups.The mean GE score increased significantly with increased treatment duration (0.42 ± 0.29 for G0 and 1.03 ± 0.52 for G3). GE scores of the lower arch were significantly higher in the anterior segment than in the posterior segment among all treatment groups. Regression analysis revealed that gender, age, oral hygiene, and treatment duration had a significant effect on GE (P0.05), while angle classification, overjet, overbite, treatment stage, bracket type, and therapeutic extraction did not show significant associations (P0.05).Gender, age, oral hygiene, and treatment duration were the most important risk factors for GE during fixed orthodontic treatment.

Purpose To examine the morphological and hemodynamic changes of the ophthalmic artery (OA) in patients with acute coronary syndrome (ACS). Methods This cross-sectional observational study included 31 patients with ACS and 10 healthy controls (HCs). The ACS subgroups were ST-segment elevation myocardial infarction (STEMI; n = 10), non-STEMI (n = 10), and unstable angina (n = 11). OA three-dimensional (3D) models were reconstructed based on computed tomographic angiography, and morphological aspects of the OA were measured quantitatively. Moreover, numerical simulation by computational fluid dynamics was used to obtain hemodynamic information of the OA. Results The study reconstructed 41 OA models. Hemodynamic simulation revealed a significant decrease in OA blood velocity in patients with ACS compared with the HCs (median velocity, 0.046 vs. 0.147 m/s; P < 0.001). No differences in the morphological data for the OA were observed. Also, no differences in the mass flow ratio of OA to the ipsilateral internal carotid artery was found. Similar differences were observed between the ACS subgroups and HCs. OA blood velocity was negatively correlated with body mass index, abdominal circumference, left ventricular ejection fraction, and triacylglycerol and was positively correlated with early to late transmitral flow velocity, N-terminal pro-brain natriuretic peptide, serum creatinine, and potassium. Conclusions The initial OA blood velocity was slower in patients with ACS and was associated with ACS-related clinical parameters. To our knowledge, this is the first study to analyze OA characteristics in ACS using 3D model reconstruction and hemodynamic simulation, providing new perspectives on the relationship between ischemic heart disease and ocular manifestations.

The DESI Legacy Imaging Surveys (http://legacysurvey.org/) are a combination of three public projects (the Dark Energy Camera Legacy Survey, the Beijing-Arizona Sky Survey, and the Mayall z-band Legacy Survey) that will jointly image ≈14,000 deg2 of the extragalactic sky visible from the northern hemisphere in three optical bands (g, r, and z) using telescopes at the Kitt Peak National Observatory and the Cerro Tololo Inter-American Observatory. The combined survey footprint is split into two contiguous areas by the Galactic plane. The optical imaging is conducted using a unique strategy of dynamically adjusting the exposure times and pointing selection during observing that results in a survey of nearly uniform depth. In addition to calibrated images, the project is delivering a catalog, constructed by using a probabilistic inference-based approach to estimate source shapes and brightnesses. The catalog includes photometry from the grz optical bands and from four mid-infrared bands (at 3.4, 4.6, 12, and 22 μm) observed by the Wide-field Infrared Survey Explorer satellite during its full operational lifetime. The project plans two public data releases each year. All the software used to generate the catalogs is also released with the data. This paper provides an overview of the Legacy Surveys project., The BASS is also supported by the External Cooperation Program of Chinese Academy of Sciences (Grant # 114A11KYSB20160057), and Chinese National Natural Science Foundation (Grant # 11433005). The Legacy Surveys imaging of the DESI footprint is supported by the Director, Office of Science, Office of High Energy Physics of the U.S. Department of Energy under Contract No. DE-AC02- 05CH11231, by the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility under the same contract; and by the U.S. National Science Foundation, Division of Astronomical Sciences under Contract No. AST-0950945 to NOAO. Travel and other support for the DECaLS and MzLS projects is provided by the National Optical Astronomy Observatory, the Lawrence Berkeley National Laboratory, and the DESI Project. This research used resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 320964 (WDTracer). J. Moustakas gratefully acknowledges support from the National Science Foundation grant AST1616414. A. Dey thanks the Radcliffe Institute for Advanced Study for their generous support during the year these surveys were initiated. A. Dey, D. J. Schlegel, and D. Lang thank the Aspen Center for Physics, which is supported by National Science Foundation grant PHY-1066293, for their hospitality and support during summer 2015 during which part of this work was conducted.

Background The coronavirus disease 2019 (COVID-19) epidemic is still ongoing, but the optimal treatment remains unclear. China adopted a series of measures, including widespread screening, strict quarantine and early treatment, combining western medicine with Chinese medicine, leading to rapid control of its spread. Nevertheless, the effects of ( combined ) Chinese medicine in reducing the toll of COVID-19 lack proof from statistics. Objective We conducted a retrospective data analysis to determine whether ( combined ) Chinese medicine is able to affect patient outcomes and to decrease the risk of death in COVID-19 patients. Methods The data were acquired by outputting the formatting information from the HIS system and then extracting and recording it in the database for complete cases. The demographics, disease onset, treatment, survival/death and all of the clinical classifications, groups and definitions were verified by specialists in the clinic, along with the research methodology and statistics, before conducting the statistical analysis. The characteristics of the cohort and the clinical symptoms and signs, prescriptions and outcomes were described and analyzed by the mean ± SD, median, interquartile range and composition ratio. Analysis of variance was used for comparisons between the measurement data sets; otherwise, the rank sum test was used. Counting data were compared between groups using the chi square test and Fisher’s exact test. Tendency matching was adopted to make the general data balance between groups. A Cox proportional hazard model was used to compare the risk of death among the different groups. Results Four centers were included in our study, and a total of 6,076 patients' clinical records were obtained after combining the data. We included 4567 cases for the descriptive statistics, and the crude case fatality rate was 3.0%. Compared with using only western medicine, (combined) Chinese medicine reduced the risk of death from COVID-19 after adjusting for other prognostic risk factors (HR = 0.135, 95% CI (0.088, 0.208)). Multivariate Cox regression also indicated that when applying the clinical classification of severe/critical, age ≥ 65 years old, coronary heart disease or chronic kidney disease and a time from onset to hospital admission of fewer than 14 days, all of these factors increased the risk of death. Conclusion (Combined) Chinese medicine can significantly reduce the risk of death from COVID-19, but the specific strategy/solution, effects and amount need further exploration in future studies.

Simple Summary Aberrant activation of the Wnt/β-catenin pathway due to APC (adenomatous polyposis coli) loss and Kirsten ras (KRAS) mutation is highly associated with malignant evolution, e.g., metastasis, of colorectal cancer (CRC). Ral guanine nucleotide dissociation stimulator-like (RGL) proteins, such as RGL2, regulate RAS activity via controlling the exchange between GTP and GDP. Although the cross-talk between β-catenin and KRAS has been reported to promote cancer metastasis, the functional role of RGL2 remains largely unknown. Here we show that RGL2 is significantly upregulated in primary tumors compared to normal tissues and serves as a poor prognostic marker in CRC patients. Cell-based and animal experiments further demonstrate that RGL2 acts as a driver to promote the metastatic progression of CRC, most likely via preventing the protein degradation of β-catenin and KRAS. Our findings not only unveil the oncogenic function of RGL2 but also provide a new strategy to combat metastatic CRC by targeting RGL2 activity. Abstract Colorectal cancer (CRC) is one of the most common cancers and results in high mortality worldwide, owing to cancer progression, i.e., metastasis. However, the molecular mechanism underlying the metastatic evolution of CRC remains largely unknown. Here, we find that the upregulation of Ral Guanine Nucleotide Dissociation Stimulator Like 2 (RGL2) is commonly detected in primary tumors compared normal tissues and is significantly associated with a poorer prognosis in CRC patients. Moreover, RGL2 expression appeared to positively correlate with the metastatic potentials of CRC cells. Whereas RGL2 knockdown dramatically suppresses the metastatic potentials of CRC cells in vitro and in vivo, RGL2 overexpression in the poorly metastatic CRC cells and reconstitution in the RGL2-silenced CRC cells enhanced and rescued the cellular metastatic ability, respectively. Computational simulation using Gene Set Enrichment Analysis program and cell-based assays demonstrated that RGL2 expression causally associated with the activity of Wnt/β-catenin signaling axis and Kirsten ras (KRAS)S, as well as the progression of epithelial-mesenchymal transition (EMT) in the detected CRC cells. Importantly, RGL2 upregulation was capable of preventing the protein degradation of β-catenin and KRAS in CRC cells. These findings suggest that RGL2 acts as a driver to promote the metastatic progression of CRC and also serves as a poor prognostic biomarker in CRC patients.

OBJECTIVES The aim of this study was to evaluate the efficacy of adjuvant chemotherapy (ACT) for thymic squamous cell carcinoma after completely resection. METHODS Patients with thymic squamous cell carcinoma treated with complete resection between January 2009 and December 2016 were retrospectively identified. Kaplan–Meier analysis was used to summarize the time-to-event variables. Univariable and multivariable Cox proportional hazards regression analyses were performed. RESULTS A total of 116 patients were analysed with 44 patients in the non-ACT group and 72 patients in the ACT group. No significant difference was found in the 5-year recurrence-free survival (RFS) rate (58.1% vs 51%, P = 0.33) or the 5-year overall survival (OS) rate (77.7% vs 67.1%, P = 0.26) between the ACT group and the non-ACT group. Masaoka stage was the only independent prognostic factor for both RFS and OS. Subgroup analysis showed significant improvement in 5-year RFS for Masaoka stage II patients (P = 0.035) and 5-year OS (P = 0.036) for Masaoka stage III patients when comparing ACT with non-ACT. No chemotherapy-related death occurred. The most frequent adverse effect higher than grade 3 was neutropenia. CONCLUSIONS For completely resected thymic squamous cell carcinoma, ACT significantly improved the 5-year RFS in Masaoka stage II patients and the 5-year OS in Masaoka stage III patients.

Object To observe the clinical effect of Q-switch Nd: YAG 1064nm laser combined with tranexamic acid on chloasma. Methods 140 cases of chloasma patients were enrolled in our clinic laser center from January 2018 to October 2018 and randomly divided into basic treatment group and combination treatment group. 70 cases in each group. Patients in the basic treatment group were treated with Q-switch Nd: YAG 1064nm laser. All patients received 10 times treatments at a 10-days interval. The combination group was treated with laser combination topical tranexamic acid, 2-4 drops twice a day for 12 weeks. Every patient should be anti-sun burn during the treatment period. After treatment, the clinical efficacy of the two groups was analyzed. Results After treatment, MASI scores of patients in the basic treatment group were significantly lower than those in the combination treatment group, and the difference was statistically significant $(\mathrm{P}\lt 0.05)$. The effective rate of combination treatment group was 81.43%, which is higher than that of the basic treatment group (65.71%). Two groups of comparison, the curative effect of the combination treatment group was better than that of the basic treatment group ($X^{2}=4.568, \mathrm{P}\lt 0.05)$. The satisfaction of the basic treatment group was 85.71%, and that of the combination treatment group was 95.7%. The satisfaction of the basic treatment group was significantly higher than that of the combination treatment group. No severe adverse reactions were observed in all patients. Conclusions The efficacy of Q-switch Nd:YAG 1064nm laser combined with tranexamic acid for the treatment of chloasma was better than that of single laser therapy. It can significantly improve clinical outcome, increase the satisfaction of patients. It is worthy of clinical application.

There is currently no drug or therapy that can cure the coronavirus disease 2019 (COVID-19), which is highly contagious and can be life-threatening in severe cases. Therefore, seeking potential effective therapies is an urgent task. An older female at the Leishenshan Hospital in Wuhan, China, with a severe case of COVID-19 with significant shortness of breath and decrease in peripheral oxygen saturation (SpO2), was treated using manual acupuncture and Chinese herbal medicine granule formula Fuzheng Rescue Lung with Xuebijing Injection in addition to standard care. The patient's breath rate, SpO2, heart rate, ratio of neutrophil/lymphocyte (NLR), ratio of monocyte/lymphocyte (MLR), C-reactive protein (CRP), and chest computed tomography were monitored. Acupuncture significantly improved the patient's breathing function, increased SpO2, and decreased her heart rate. Chinese herbal medicine might make the effect of acupuncture more stable; the use of herbal medicine also seemed to accelerate the absorption of lung infection lesions when its dosage was increased. The combination of acupuncture and herbs decreased NLR from 14.14 to 5.83, MLR from 1.15 to 0.33 and CRP from 15.25 to 6.01 mg/L. These results indicate that acupuncture and Chinese herbal medicine, as adjuvants to standard care, might achieve better results in treating severe cases of COVID-19.

To investigate effects of agomelatine and mirtazapine on sleep disturbances in patients with major depressive disorder. A total of 30 depressed patients with sleep disturbances, 27 of which completed the study, took agomelatine or mirtazapine for 8 weeks. Subjective scales were administered, and polysomnography was performed at baseline and at the end of week 1 and 8. Functional magnetic resonance imaging was performed at baseline and at the end of week 8. Compared with baseline, scores on the Hamilton Depression Scale, Hamilton Anxiety Scale, Pittsburgh Sleep Quality Index, Sleep Dysfunction Rating Scale, and Insomnia Severity Index after 8 weeks of treatment significantly decreased in both groups, with no significant differences between groups, accompanied by significant increases in total sleep time, sleep efficiency, and rapid eye movement (REM) sleep and significant decrease in wake after sleep onset. Mirtazapine treatment increased N3 sleep at week 1 compared with agomelatine treatment, but this difference disappeared at week 8. The increases in the percentage and duration of N3 sleep were positively correlated with increases in connectivity between right dorsal lateral prefrontal cortex (dlPFC) and right precuneus and between left posterior cingulate cortex and right precuneus in both groups, respectively. Functional connectivity (FC) between right dlPFC and left precuneus in mirtazapine group was higher compared with agomelatine group after 8 weeks of treatment. These findings indicated that both agomelatine and mirtazapine improved sleep in depressed patients, and the effect of mirtazapine was greater than agomelatine with regard to rapidly increasing N3 sleep and gradually improving FC in the brain.

Background Aggressive angiomyxoma (AA) is a rare tumor that typically occurs in the pelvis and perineum, most commonly in women of reproductive age. However, no para-ureteral AA has been reported according to the literature. Case presentation We herein describe the first case of para-ureteral AA. A 62-year-old male presented to our institute in March 2017 with a para-ureteral mass that was 15 mm in diameter incidentally. No symptom was observed and laboratory analysis was unremarkable. Magnetic resonance and computed tomography imaging showed a non-enhancing mass abutting the left ureter without causing obstruction. Laparoscopic resection of the mass was performed without injury to the ureter. Pathologic and immunohistochemical results were consistent with AA. Till now, no recurrence was noticed. Conclusions We reported a rare case of para-ureteral AA, along with a literature review. Early diagnosis, proper surgical plan and long-term close follow-up is recommended for its high risk of recurrence and malignant potential.

Visceral pain is one of the leading causes for abdominal pain in gastroenterological diseases and is still hard to treat effectively. Bulleyaconitine A (BAA) is an aconitine analog and has been used for the treatment of pain. Our previous work suggested that BAA exerted analgesic effects on neuropathic pain through stimulating the expression of dynorphin A in spinal microglia. Here, we investigated the inhibitory effect of BAA on visceral pain and examined whether the expression of dynorphin A in spinal microglia was responsible for its effects. We found that BAA produced significant antivisceral pain effect induced by acetic acid through stimulating dynorphin A expression in spinal microglia. In addition, anxiety and chronic visceral pain are highly prevalent comorbid conditions in clinical research, which is still a problem to be solved. We also aimed to evaluate the effects of BAA on anxiety. A comorbidity model with characteristics of both chronic visceral pain and anxiety was developed by colorectal injection of 2,4,6-trinitrobenzene sulfonic acid and the induction of heterotypic intermittent chronic stress protocol. In comorbid animals, BAA exerted great antianxiety effects. Meanwhile, the antianxiety mechanism of BAA was different with the antivisceral pain mechanism of BAA. In conclusion, our study demonstrated, for the first time, that BAA exerted marked antivisceral pain and antianxiety effects, which expands the analgesic spectrum and clinical application of BAA. Furthermore, it also it provides a better guidance for the clinical use of BAA.

Purpose This study aimed to evaluate the efficacy and safety of intensity modulated radiation therapy (IMRT) for pleural recurrence of thymoma that was not suitable for surgery and had progressed after chemotherapy. Materials and Methods From February 2012, consecutive patients with pleural recurrence of thymoma were prospectively enrolled. Due to dose restrictions to normal tissue (lung, liver, and kidney), 3 different levels of radiation doses (30 Gy, 40 Gy, and 50 Gy) were prescribed for pleural lesions of different sizes and locations, with a daily fraction dose of 2 Gy. The objective response rate, local control time (LCT), overall survival time, and toxicity were recorded, respectively. Results By August 2016, 31 patients had completed the IMRT treatment. There were 21 male and 10 female patients, with a median age of 49 (range, 22-70) years. B3 thymoma was the major (62%) tumor subtype observed. During the median follow-up of 48 (24-70) months, the objective response rate was 97%, and the median LCT was 49 (95% confidence interval, 40.4-58.1) months. However, 29 (93.5%) patients developed out-of-field recurrence, among whom 10 (32%; 30 Gy, n = 7; 40 Gy, n = 3) developed both out-of-field and in-field recurrence. The median progression-free survival was 19 months, and no in-field recurrence occurred in the 50 Gy group. Moreover, a higher dose was related to a longer LCT. No toxicities higher than a grade 4 occurred after IMRT within the normal-tissue dose limitation. The 5-year overall survival of the patients was 81%. Conclusions IMRT for pleural recurrence may act as an alternative treatment when surgery is not feasible, with a higher dose resulting in a longer LCT. In this study, out-of-field recurrence was considerably common, but repeated IMRT for new recurrence should be cautiously carried out due to the high risk of radiation-induced pneumonitis.

Neurotoxicity is one of the major pathological changes in multiple neurological disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD), the second popular neurodegenerative disease in aged people. It is known that the AD and PD share the similar neuropathological hallmarks, such as the oxidative stress, loss of specific neurons, and aggregation of specific proteins. However, there are no effective therapeutic drugs for both AD and PD yet. Oxytocin (OXT) is a small peptide with 9 amino acids that is neuroprotective to many neurological disorders. Whether OXT administration confers neuroprotection to 1-methyl-4-phenyl-1, 2, 3, 6- tetrahydropyridine (MPTP)-induced neurotoxicity in mice are still not known. In this study, we first found that the OXT levels are decreased in MPTP mice. Supplementation with OXT effectively rescues the locomotor disabilities and anxiety-like behaviors in MPTP mice. OXT also alleviates the hyperphosphorylation of α-synuclein at S129 site and the loss of dopaminergic neurons in the substantia nigra pars compacta, as well as the oxidative stress in the MPTP mice, and alleviates both oxidative stress and cell cytotoxicity in vitro. Furthermore, we found that OXT could inhibit the miR-26a/DAPK1 signal pathway in MPTP mice. In summary, our study demonstrates protective effects of OXT in MPTP mice and that miR-26a/DAPK1 signaling pathway may play an important role in mediating the protection of OXT.

Background: Patients with depression often suffer from circadian rhythm disruptions, such as insomnia and a lower amplitude of daily rhythms of locomotor activity. However, whether circadian disorders precede depression and act as a predictor for subsequent depression have not been unanimously approved. In light of increasing evidence of an association between disrupted circadian rhythms and affective symptoms, a meta-analysis was conducted to examine the effect of circadian disruptions on incident depression. Methods: A systematic search was performed in PubMed, Embase, Web of Science, PsycINFO, PsycArticles, CINAHL database. The search results were restricted to be published in English up to April 10, 2020.Reference lists from included studies and relevant reviews were also screened. We included longitudinal cohort studies that examined the predictive role of all various types of circadian disruption in incident depression. Two reviewers independently extracted information on study design, participants’ characteristics and diagnostic criteria for circadian disruption and depression. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effect models were applied to all meta-analyses given potential heterogeneity. For insomnia, subgroup analyses were performed based on subject’s characteristics, insomnia symptom domains and numbers and the investigated methods. Pool-effect estimates of relative risks to develop incident depression in groups with circadian disruption compared to groups without. This study is registered with PROSPERO, CRD42020179135. Findings: A total of 49 studies were eligible for this meta-analysis. Of 49 eligible studies, included types of circadian disruption were sleep disturbances (n = 45), chronotype (n = 2), cortisol awakening response (n = 1) and rest - activity rhythm (n = 1). Insomnia, hypersomnia, excessive daytime sleepiness (EDS), short sleep duration, obstructive sleep apnea (OSA), restless legs syndrome (RLS), an evening preference, heightened levels of cortisol in awakening response and low robustness of rest - activity rhythm all acted as significant predictors of occurrence of depression. Among insomnia subtypes, difficulty initiating sleep (DIS) and difficulty maintaining sleep (DMS) predicted future depression. Of note, persistent insomnia (OR: 5.02) contributed to more than two - fold risk of incident depression compared to insomnia (OR: 2.34). Moreover, insomnia symptom numbers were associated with incident depression in a gradient trend. Interpretation: Different types of circadian disorders act as risk factors of onset of depression, which clinicians should be informed of. Future research should be aimed to determine the casual relationship between other types of circadian disorders and onset of depression, and moreover to further elucidate the underlying mechanisms. Funding Statement: This work was supported in part by the National Natural Science Foundation of China (no. 81871071 and 81171251) and Beijing Municipal Natural Science Foundation (no. 7162101). Declaration of Interests: All of the authors declare no conflict of interest.

Background. Visceral pain is one of the most common types of pain and particularly in the abdomen is associated with gastrointestinal diseases. Bulleyaconitine A (BAA), isolated from Aconitum bulleyanum, is prescribed in China to treat chronic pain. The present study is aimed at evaluating the mechanisms underlying BAA visceral antinociception. Methods. The rat model of chronic visceral hypersensitivity was set up by colonic perfusion of 2,4,6-trinitrobenzene sulfonic acid (TNBS) on postnatal day 10 with coapplication of heterotypic intermittent chronic stress (HeICS). Results. The rat model of chronic visceral hypersensitivity exhibited remarkable abdominal withdrawal responses and mechanical hyperalgesia in hind paws, which were dose-dependently attenuated by single subcutaneous of administration of BAA (30 and 90 μg/kg). Pretreatment with the microglial inhibitor minocycline, dynorphin A antiserum, and κ-opioid receptor antagonist totally blocked BAA-induced visceral antinociception and mechanical antihyperalgesia. Spontaneous excitatory postsynaptic currents (sEPSCs) in spinal dorsal horn lamina II neurons were recorded by using whole-cell patch clamp. Its frequency (but not amplitude) from TNBS-treated rats was remarkably higher than that from naïve rats. BAA (1 μM) significantly reduced the frequency of sEPSCs from TNBS-treated rats but not naïve rats. BAA-inhibited spinal synaptic plasticity was blocked by minocycline, the dynorphin A antiserum, and κ-opioid receptor antagonist. Dynorphin A also inhibited spinal synaptic plasticity in a κ-opioid receptor-dependent manner. Conclusions. These results suggest that BAA produces visceral antinociception by stimulating spinal microglial release of dynorphin A, which activates presynaptic κ-opioid receptors in afferent neurons and inhibits spinal synaptic plasticity, highlighting a novel interaction mode between microglia and neurons.

Objective Nationwide data on eating disorders (EDs) among East Asian populations are scarce. This study aimed to estimate the prevalence, incidence, and psychiatric comorbidities of EDs in Taiwan. Method Drawing from the National Health Research Institute database, we identified the study subjects aged 11-34 years who received an ED diagnosis during ambulatory visits or hospitalization from 2001 to 2012. We analyzed the subjects by age and gender. Diagnoses for comorbid psychiatric disorders were entered in the analysis only if they occurred within 1 year before or after the ED diagnosis date. Rates were age- and sex-adjusted to the average population within the study period. Results The estimated mean annual incidence was approximately 11.11 (95% CI 10.51-11.72) per 100,000 residents, and the 1 year prevalence was 20.87 (95% CI 20.05-21.70) per 100,000 residents, with evidence of female predominance (female/male ratio = 10.95, 95% CI = 8.97-13.36). Incidence and prevalence peaked at ages 20-24 in females and at ages 25-29 in males. Both rates nearly doubled within a decade. Specifically, the anorexia nervosa trend recently stabilized in females and decreased in males, while that for bulimia nervosa increased in both females and males. The most common comorbid diagnoses were anxiety (53%) and major depressive disorders (22%). Discussion The incidence and prevalence of EDs were lower in Taiwan than in Western countries. However, these rates were rapidly rising, notably in males. The majority of Taiwanese ED patients also received a diagnosis for various psychiatric comorbidities, a finding worthy of clinical attention.

Objective: To evaluate the clinicopathologic characteristics of the long-time survivals and construct a clinical nomogram using the Surveilance, Epidemiology, and End Results (SEER) database. Materials and Methods: Information of patients diagnosed with M1 stage esophageal cancer from 2010-2014 was retrieved from SEER database. Patients with unknown information of AJCC TNM stage or metastatic sites or marital status or surgery or survival were excluded. Demographic and clinicopathologic characteristics were compared between LTS (long time survivals: patients who have survived for no less than 2 years) and STS (shorter time survivals: patients who have survived for less than 2 years). Cox regression analysis was performed to evaluate prognostic factors. A nomogram comprising demographic and clinicopathologic factors was established to predict 1-year survival and 2-year survival for patients with M1 diseases. Results: A total of 2981 patients from the SEER database were included for analysis. Compared with the STS, married people and patients with well differentiated tumors or oligometastatic site were more likely to be LTS. Also, LTS were associated with significantly less bone metastasis and more surgery. The OS nomogram, which had a c-index of 0.633, was based on the eleven variables: gender, age, marital status, T stage, N stage, histology, grade, number of important metastatic organs and primary surgery. Conclusions: Married patients, patients with well differentiated tumors, patients with oligometastatic site, patients without bone metastasis or liver metastasis and those who underwent surgery are associated with long time survivals. We developed a nomogram predicting 1- and 2-year OS and CSS for M1 stage esophageal cancer. The prognostic model may improve clinicians' abilities to predict individualized survival and to make treatment recommendations.

Background: Thymic carcinoma (TC) is a rare mediastinal tumor, and patients with stage IV TC have a poor prognosis. No optimal chemotherapeutic regimen has yet been established. In this study, we evaluated the efficacy and safety of S-1 as a salvage mono-therapy in stage IV TC. Methods: Patients with histologically confirmed stage IV TC were enrolled in this study when front-lined chemotherapy failed. S-1 capsules were orally taken twice a day. The daily dose was prescribed in three levels (80, 100, 120 mg) based on body surface area (BSA). One cycle of treatment consists of 4 weeks of drug use and 2 weeks of rest. The cycle was repeated until tumor progressed or intolerable toxicity occurred. The response rate, progression-free survival (PFS), overall survival (OS), and toxicity were evaluated. Results: Forty-four patients with stage IV TC were included between January 2013 and July 2017. Squamous cell carcinoma accounted for 84% of cases (37/44). There were 22 males and 22 females with a median age of 57 years (27–78 years). S-1 was prescribed at a dose of 80 mg for 18 (41%) patients, 100 mg for 17 patients (38%), and 120 mg for 9 patients (21%). The median number of cycles of administrated per patient was 3 [1–32]. Among 44 patients, 13 (30%) achieved a partial response, 22 (50%) remained stable disease, and 9 (20%) showed a rapid progression. With a median follow-up time of 14 months, the median PFS and OS of the whole group were 6 (95% CI, 7.0–13.9) months and 15 (95% CI, 13.2–21.6) months, respectively. For the 13 patients who showed response to S-1, the median PFS was 22 (95% CI, 15.5–30) months. Anorexia was the most common side effect, but all cases were mild. Other toxicities of grade ≥3 were bone marrow suppression (n=6) and rash (n=1). No drug-related deaths occurred. Conclusions: S-1 is a safe and effective treatment for stage IV TC as a salvage monotherapy. It is especially effective in disease control when the tumor shows response to S-1.

To investigate the incidence of tubulointerstitial injury in lupus nephritis (LN) and to examine clinicopathological factors that could indicate the presence of tubulointerstitial injury.This study included 98 patients with LN. Clinical data and the pathological results of the initial renal biopsy were collected.The frequency of each tubulointerstitial injury parameter was over 50%, except for the interstitial edema, in the 98 patients investigated in this study. The most frequently detected tubulointerstitial injury parameter was tubular atrophy in this study. Neutrophil infiltration/karyorrhexis, wire loop lesion, and arteriosclerosis were observed frequently in patients with tubulointerstitial injuries. High serum creatinine and blood urea nitrogen (BUN) were observed more frequently in patients with tubulointerstitial injuries except tubular degeneration. The multivariable regression analysis showed a relationship between neutrophil infiltration/karyorrhexis and interstitial fibrosis/tubular degeneration, a relationship between wire loop lesion and tubulointerstitial inflammation/edema, and a relationship between arteriosclerosis and tubulointerstitial injuries (except interstitial edema). Patients with tubular degeneration had lower D-Dimer levels compared with those without. Patients with interstitial fibrosis had higher blood leukocyte counts than those without. The rate of low response to therapy was 13% among those without tubulointerstitial inflammation, but 35% in those with interstitial inflammation (P = 0.03).Acute and chronic renal tubulointerstitial lesions are often found along with glomerular and vascular lesions. Immune and vascular factors are probably involved in tubulointerstitial injuries. Tubulointerstitial inflammation may be the initiator of chronic renal injury and may predict response to therapy.Key Points•To provide a theoretical basis for tubulointerstitial injury in LN.

In this article, the visual realism of designed pictures on computer screens is studied by investigation and brain-wave analyses. The practical electroencephalogram (EEG) measurement is always time-varying and fluctuating so that conventional statistical techniques are not adequate for analyses. This study proposes a new scheme based on “fingerprinting” to analyze the EEG. Fingerprinting is a technique of probabilistic pattern recognition used in electrical engineering, very like the identification of human fingerprinting in a criminal investigation. The goal of this study was to assess whether subjective preference for pictures could be manifested physiologically by EEG fingerprinting analyses. The most important advantage of the fingerprinting technique is that it does not require accurate measurement. Instead, it uses probabilistic classification. Participants’ preference for pictures can be assessed using fingerprinting analyses of physiological EEG measurements.

Background: Surgical resection remains the mainstay of treatment for patients with early-staged thymic tumors, while chemotherapy is most commonly used in stage IV cases. As for locally advanced thymic tumors, especially those unsuitable for surgery, the optimal therapy is still controversial. Thus, we conducted this retrospective study by comparing three nonsurgical treatment modalities to find some clues. Methods: Three treatment modalities were used in 42 patients from October 2000 to December 2010, including radiotherapy (RT) alone, sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT). Objective response rate (ORR), overall survival (OS) and toxicity of the three regimens were compared accordingly. Results: The ORR in all 42 patients was 61.9%, and 5-year OS was 46%. The ORR of RT, SCRT and CCRT were 43.8%, 50% and 87.5%, respectively (RT vs. SCRT, P=0.692; RT vs. CCRT, P=0.009; SCRT vs. CCRT, P=0.051). The 5-year OS of RT, SCRT and CCRT were 30%, 50% and 61.9%, respectively. (RT vs. SCRT, P=0.230; RT vs. CCRT, P=0.011; SCRT vs. CCRT, P=0.282). Eleven patients developed neutropenia of grade 3–4, with 7 in CCRT group and 4 in SCRT, respectively. Nine patients experienced esophagitis of grade 3 with 2 in RT, 3 in SCRT and 4 in CCRT. There were also two cases of grade 3 radiation induced pneumonitis in CCRT group. No life-threatening side effects were noted. Conclusions: When used to treat locally advanced thymic tumors unsuitable for surgery, CCRT performed more favorably than RT alone or SCRT in both tumor response and long time survival, but probably with the increasing risk of pulmonary damage. CCRT may offer the best chance of disease control in the management of locally advanced disease.

We demonstrate low threshold lasing oscillation in a photonic crystal (PhC) laser by using tert-butyl Rhodamine B (t-Bu-RhB) doped gain media. Lactonic t-Bu-RhB is synthesized to improve doping concentration in polymethylmethacrylate (PMMA) films, and then isomerized to the zwitterion form to achieve highly fluorescent gain medium. The t-Bu-RhB doped PMMA film is sandwiched by a pair of polystyrene colloidal crystals to construct a PhC resonating cavity. Single-mode laser oscillation at 592 nm is observed when the PhC resonating cavity is pumped by a Nd:YAG laser. The lasing threshold is 0.12 MW cm(-2) utilizing 6.9 wt% t-Bu-RhB doped PMMA films, which is only 1/60 of that with 3 wt% t-Bu-RhB doped PMMA films. The concentration-dependent lasing action is attributed to different gain factors of the t-Bu-RhB doped PMMA films. Furthermore, a spatially and spectrally coherent laser beam from the PhC resonating cavity is verified by exploring the far-field image and angular dependence of the lasing emission. The approach provides a facile and efficient strategy to reduce the lasing threshold for fabricating low threshold PhC lasers.

Background Hospital readmissions caused by relapse in patients with schizophrenia are associated with prognosis. Identifying individuals at high risk of readmission and providing interventions to lower the readmission rate are important. Methods Patients with schizophrenia who were hospitalized for the first time were recruited from the National Health Insurance Research Database from 2001 to 2010 (n = 808, mean age 28.9 years) and compared with matched controls. Data on the demographics, cost, and utilization of medical resources of patients who were readmitted were compared with non-readmitted patients. The readmission time curve was analyzed by the Kaplan–Meier method. Result 570 (70.5%) patients were readmitted within 10 years; the median time between admissions was 1.9 years, and 25% of subjects were readmitted within 4 months of the first hospitalization. There were no significant differences in age, gender, or length of hospitalization between the readmission and non-readmission groups. Taking into account all psychiatric medical services, the readmission group had a significantly higher mean frequency of care and a greater medical cost than the non-readmission group and matched controls. However, there were no significant differences with regard to non-psychiatric medical services. Conclusion Schizophrenia has a high rate of readmission and high medical cost in naturalistic settings. In addition to the traditional hospital-based treatment model for patients with schizophrenia, the development of an effective intervention program is important, especially in the early years of the disease.

To estimate the impact of peri-prostatic fat (PPF) measurements using preoperative magnetic resonance imaging on the prediction of prostate cancer (PCa) with transrectal ultrasound-guided biopsy.We performed a retrospective 2-center study on 660 consecutive patients receiving transrectal ultrasound-guided biopsy-biopsy from June 2016 to October 2018. Pathologic and immunohistochemical characteristics were collected. PPF measurements including PPF area (PPFA) and PPFA to prostate area (PA) ratio (PPFA/PA) were assessed by preoperative staging magnetic resonance imaging. Clinical variables were correlated with Gleason score by using Spearman (ρ) correlation coefficients. Multivariable analysis was performed to identify independent predictors of PCa. The diagnostic performance was estimated using ROC curves.The Gleason score was significantly correlated with age (ρ = 0.114, P = 0.035), prostate-specific antigen (PSA) (ρ = 0.482, P0.001), PIRADS scoring (ρ = 0.403, P0.001) and PPFA/PA (ρ = 0.238, P0.001). Multivariate analysis revealed that PPFA/PA, age, digital rectal examination, family history of PCa, PSA, and PIRADS scoring were independently predictive of PCa. The ROC AUC to detect PCa or clinically significant PCa (CS-PCa; Gleason Score 3 + 4 or greater) improved with the addition of PPFA/PA (PCa: 0.93 vs. 0.89; CS-PCa: 0.92 vs. 0.90).PPFA/PA is an independent predictor for PCa along with age, digital rectal examination, family history of PCa, PSA, and PIRADS scoring. PPF measurements especially PPFA/PA may help detect PCa or CS-PCa, thus helping improve PCa risk stratification and screening to avoid unnecessary biopsies.

Risperidone long-acting injection (RLAI), the first licensed, long-acting second-generation antipsychotic (SGA), has not yet been studied in terms of its effectiveness compared with first-generation antipsychotic (FGA) LAIs.The differences in the effectiveness of RLAI and two other FGA LAIs, haloperidol and flupentixol, were assessed by conducting a one-year pre-post study based on the Taiwanese National Health Insurance Research Database. Effectiveness was defined as reduced medical care utilization and relapse prevention.A decreased number of relapses were identified in the haloperidol injection group in the post-LAI period than in the pre-LAI period (Wilcoxon signed rank test, p0.05). The RLAI group had the largest number of acute admissions and relapses, the longest duration of admission (Wilcoxon signed rank test, p0.005), and the lowest utilization of anticholinergic agents, such as benzodiazepine (BZD) and SGAs (except oral risperidone), among all of the LAI groups in the post-LAI period.According to the results of this observational study, we suggest that the effectiveness of RLAI is not superior to that of FGA (haloperidol or flupentixol) LAIs, but that RLAI might have fewer adverse effects.

Background: Oxytocin interacts with the dopaminergic system, which plays a role in addiction behaviors. The association between oxytocin and addiction was confirmed in animal studies. Novelty seeking is one of the predictors and indicators of drug addiction. The aim of the present study was to probe the association between oxytocin and novelty seeking. Methods: The study was conducted in a methadone maintenance therapy clinic of a medical center in Taiwan; 77 patients with heroin dependency were enrolled. Plasma oxytocin was measured using an ELISA kit. Novelty seeking was measured using an established instrument (the novelty seeking subscale of the Tridimensional Personality Questionnaire). Results: A significant negative association (ρ = -0.27, p = 0.02; r = -0.34, p = 0.003) between the blood level of plasma oxytocin and novelty seeking was found. This association was significant after controlling the effects of perceived social support and the dosage of methadone (r = -0.32, p = 0.006). Conclusion: The negative association between oxytocin and novelty seeking may provide insight into future treatments for addiction.

The aim of this study was to examine the metabolic parameters, including body mass index (BMI), homeostasis model assessment-estimated insulin resistance (HOMA-IR), homeostasis model assessment-estimated pancreatic β-cell function (HOMA-β), and lipid plasma level, in medicated patients with major depressive disorder (MDD) and to assess factors related to metabolic parameters in patients with MDD. 121 patients with MDD and 63 controls were recruited. The Hamilton Depression Rating Scale (HDRS), Wisconsin Card Sorting Test (WCST), Continuous Performance Test (CPT), and Finger-Tapping Test (FTT), were administered. BMI, HOMA-IR, and HOMA-β were calculated as modifiable metabolic parameters. The FTT results and BMI in depressed patients were significantly poorer and lower, respectively, than those of the controls. However, no significant differences were noted between MDD patients and controls included metabolic parameters and other neuropsychological tests. Among depressed patients, higher BMI is significantly related with lower education, no tobacco use, and male. The result demonstrated metabolic parameters could be neutral among medicated patients with MDD, particularly in non-elderly Asian individuals. The deficits of psychomotor speed could be more prominent than other cognitive alterations in patient with MDD.

The rapidly increasing diabetes mellitus (DM) is becoming a major global public health issue. Traditional Chinese medicine (TCM) has a long history of the treatment of DM with good efficacy. Huangqi and Huanglian are one of the most frequently prescribed herbs for DM, and the combination of them occurs frequently in antidiabetic formulae. However, the synergistic mechanism of Huangqi (Radix Astragali) and Huanglian (Rhizoma Coptidis) has not been clearly elucidated. To address this problem, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the synergistic mechanisms of these two herbs. Forty-three active ingredients of Huangqi (mainly astragalosides and isoflavonoids) and Huanglian (primarily isoquinoline alkaloids) possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 50 DM-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as GLUT2, NOS2, PTP1B, and IGF1R were mainly involved in PI3K-Akt signaling pathway, insulin resistance, insulin signaling pathway, and HIF-1 signaling pathway, and were mainly located in retina, pancreatic islet, smooth muscle, immunity-related organ tissues, and whole blood. The contribution index of every active ingredient also indicated five compounds, including berberine (BBR), astragaloside IV (AIV), quercetin, palmatine, and astragalus polysaccharides, as the principal components of this herb combination. These results successfully explained the polypharmcological and synergistic mechanisms underlying the efficiency of Huangqi and Huanglian for the treatment of DM and its complications.

International audience; In-air gestural interfaces are gaining popularity due to the increasing availability and low cost of gesture recognition hardware. However, the current literature mainly focuses either on the young adult user group or, when focusing on older people, most studies limit the focus to physical activity or gaming contexts. The suitability of in-air gestural interactions for seniors to control graphical user interfaces in general remains largely unknown. Moreover, since gestural interfaces are considered easy and natural to use, they may represent an advantageous interaction modality for older people. In this study, the authors evaluate the usability of in-air hand gestures for seniors to interact with generic graphical user interfaces. A user study was conducted with 40 participants, where two types of tasks were evaluated: navigation and selection. For each task, two alternative gestures were evaluated: Swipe and Grab and Drag for navigation tasks; Point and Hold and Point and Push for selection tasks. Both qualitative and quantitative feedbacks were gathered, and then, each alternative gesture was systematically compared. Almost all participants (97 %) completed the navigation and selection tasks with at least one gesture, finding this type of interaction enjoyable to use. From the results and observations, the authors propose a set of design implications that future developers can take into account when developing hand gestural interactions for older people.

Background: Animal studies have demonstrated that oxytocin can influence addiction behaviors and might interact with the dopaminergic system, which is a key component of addiction behaviors. However, related evidence from clinical studies is scarce. The aim of our study was to explore the relationship between plasma oxytocin level and heroin craving among patients receiving methadone maintenance treatment, and to ascertain whether this relationship is moderated by novelty-seeking. Methods: The study was conducted in a methadone maintenance therapy clinic of a medical center in Taiwan. Seventy-seven patients with heroin addiction were enrolled. Plasma oxytocin was measured using an ELISA kit. Craving was assessed using an established instrument, the Chinese Craving Scale. Results: A significant negative association was found between the plasma oxytocin level and craving score, which remained robust after controlling the effects of social support and low-density lipoprotein cholesterol. An interaction between oxytocin and novelty-seeking indicated that this relationship was stronger among patients with a lower level of novelty-seeking. Conclusion: This finding may be taken into account in future studies and may provide a basis for the development of potential treatment for addiction. The effect of oxytocin for the treatment of opioid dependence might be modulated by some psychological factors.

Hepatic encephalopathy, ascites, and variceal bleeding are the three major complications of cirrhosis. It is well known that cirrhosis is the most important risk factor of hepatocellular carcinoma (HCC). However, little is known about whether the severity of liver cirrhosis has an effect on the incidence of HCC. This population-based cohort study aimed to explore the association between complicated cirrhosis and HCC, and identify the risk factors of HCC in patients with complicated cirrhosis. Data of the years 1997-2011 were extracted from the National Health Insurance Research Database of Taiwan. A total of 2568 patients with complicated cirrhosis without HCC at baseline were enrolled. After propensity score matching, another 2568 patients with non-complicated cirrhosis were included. Hazards Cox regression analysis by using a competing risk regression model to control for possible confounding factors was utilized to estimate the association of the complications of liver cirrhosis with the risk of HCC. We observed by using competing risk analysis that the adjusted hazard ratio (HR) for developing HCC during the follow-up period after the initial hospitalization was higher among the patients with baseline complicated cirrhosis than in those with uncomplicated cirrhosis (HR, 1.23; 95% confidence interval, CI, 1.10-1.37, p

The impact of adjuvant acid suppression via proton pump inhibitors or histamine-2 receptor antagonists after endoscopic variceal ligation remains uncertain. We therefore aimed to evaluate the effect of adjuvant acid suppression on the rebleeding and mortality rates in patients who received endoscopic variceal ligation and vasoconstrictor therapy for bleeding esophageal varices. Data from 1997 to 2011 were extracted from the National Health Insurance Research Database in Taiwan. A total of 1576 cirrhotic patients aged > 18 years with a primary diagnosis of acute esophageal variceal bleeding who received endoscopic variceal ligation therapy were screened. After strict exclusion, 637 patients were recruited. The exclusion criteria included patients with gastric variceal bleeding, failure in the control of bleeding, mortality within 12 hours, and history of hepatocellular carcinoma or gastric cancer. Patients were divided into two groups: the vasoconstrictors group (n = 126) and vasoconstrictors plus acid suppression group (n = 511). We observed that the rebleeding and mortality rates were not significantly different between 2 groups during hospitalization and the 15-year follow-up period after discharge. A Charlson score ≥3 (odds ratio: 2.42, 95% confidence interval: 1.55 ~3.79, P = 0.0001), presence of hepatitis C virus (odds ratio: 1.70, 95% confidence interval: 1.15 ~2.52, P = 0.0085), and cirrhosis (odds ratio: 1.69, 95% confidence interval: 1.08 ~2.66, P = 0.0229) were the independent risk factors of mortality after discharge. In conclusion, the results of the current study suggest that adjuvant acid suppression prescription to patients who received endoscopic variceal ligation and vasoconstrictor therapy for bleeding esophageal varices may not change the rebleeding and mortality outcomes compared to that for those who received endoscopic variceal ligation and vasoconstrictor agents without acid suppression.

Although a few studies have investigated the risks of peptic ulcer bleeding (PUB) in cirrhotic patients, large population-based studies on in-hospital and long-term reports on recurrent PUB in a cohort of cirrhotic patients are lacking. This 12-year nationwide cohort study aimed to investigate the risks of in-hospital and long-term rebleeding and mortality in cirrhotic patients and to identify possible risk factors. Patient data from 1997 to 2008 were extracted from the National Health Insurance Research Database in Taiwan. A total of 15,575 patients who were discharged with a diagnosis of PUB were identified after strict exclusions (n = 2889). Among them, patients with cirrhosis (n = 737) and those with chronic hepatitis (n = 1044) were compared to propensity-score matched normal controls at a ratio of 1:1. Accumulated in-hospital and long-term follow-up PUB-free survival rates were analyzed in patients with cirrhosis, patients with chronic hepatitis, and matched controls. Cox proportional hazards regression was used to identify each independent risk factor. Compared with matched controls, patients with cirrhosis exhibited a 2.62-fold (95% CI: 1.74–3.92) higher risk of developing in-hospital rebleeding, but the risk of long-term rebleeding was comparable between cirrhotic patients and matched controls (hazard ratio: 1.29, 95% CI: 0.8–2.09). On the other hand, no significant difference was observed in in-hospital and long-term rebleeding between chronic hepatitis patients and matched controls. We compared the survival rates of cirrhotic and chronic hepatitis patients to that of matched controls. After propensity score matching, both cirrhotic and chronic hepatitis patients showed significantly lower survival than the matched controls (P < 0.0001 and 0.033, respectively) during the 12-year follow-up period. However, in-hospital and long-term rebleeding rates were not significantly different between chronic hepatitis patients and matched controls (P = 0.251 and 0.474, respectively). In conclusion, liver cirrhosis increased health care expenses in patients with PUB and these patients exhibited higher recurrent bleeding rate than non-cirrhotic patients during hospitalization. Cirrhosis and chronic hepatitis are independently associated with an increased long-term mortality when compared with patients without liver disease.

A man developed with multiple warts on his hands and the inner canthus of his left eye. We applied local hyperthermia on a single target lesion on his hand at a surface temperature of 44°C for 30 minutes on Days 1, 2, 3, 17, and 18. All the lesions treated with or without heat cleared 8 weeks after the last treatment. Treatment of a target lesion resolved all other untreated lesions, a fact suggestive that local hyperthermia could induce activation of specific immunity against human papillomavirus on the lesional skin, which lead to resolution of all the warts.

The long noncoding (lnc)RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), plays a crucial role in the development of hepatocellular carcinoma (HCC). However, potential genetic variants (single nucleotide polymorphisms, SNPs) in MALAT1 that affect the susceptibility and progression of HCC have rarely been explored. Three tagging SNPs, viz., rs3200401 C > T, rs619586 A > G, and rs1194338 C > A, in MALAT1 were genotyped by a TaqMan allelic discrimination assay in 394 HCC patients and 1199 healthy controls. A stratified analysis showed that younger patients ( Furthermore, analyses of clinical datasets revealed that MALAT1 expression level was gradually unregulated during HCC development from normal liver, cirrhotic liver, dysplastic liver to HCC and correlated with poor survival rates in HCC patients, especially in the hepatitis virus-infected population.

A variety of medications and procedures are available for the treatment of warts, but it appeared the treatment response in systemic lupus erythematosus (SLE) patients is poor. It is necessary to investigate the feasibility, safety and efficacy of local thermotherapy for extensive viral warts.A SLE patient on systemic steroid developed extensive viral warts on both her hands and feet for months. She had a high score of SLE Disease Activity Index (SLEDAI), up to 30, and was extensively treated with high and prolonged dosage of corticosteroid and intermittent use of cyclophosphamide. We applied local hyperthermia at 44 °C on a target lesion for 30 min on days 1, 2, 3, 17, 18, a protocol which has been successfully used in treating viral warts. There was no sign of clinical response in a 3-month follow-up. Then we treated the patient on a once-a-week protocol.All the lesions cleared in ten weeks and there was no sign of recurrence.This observation suggests that more intensive local hyperthermia is required for clearing viral warts in SLE.

Introduction This study aimed to evaluate the long-term efficacy of multimodality therapy for patients with type B3 thymoma. Methods A total of 188 consecutive patients with type B3 were treated in our hospital from January 2001 to December 2010. One hundred seventy-seven patients who had been treated with curative intent were retrospectively analyzed. According to World Health Organization Classification, all patients were pathologically confirmed as type B3. Distribution of Masaoka stages I, II, III, and IV was 35 (19.8%), 20(11.3%), 78 (44.1%), and 44 (24.8%), respectively. Myasthenia gravis coexisted in 34% of patients. Results After a mean follow-up of 49 months (7–135 months), the 10-year overall survival (OS) rates were 65% (89%, 86%, 61%, and 42% in stage I, II, III, and IV, respectively). One hundred five patients patients (102 patients with R0 resection and 3 with complete response after radiotherapy) were analyzed for freedom from recurrence (FFR). The 5- and 10-year FFR rates were 91% and 73% (100%, 94%, 84%, 71% and 100%, 94%, 56%, N/A in stages I, II, III, and IV, respectively. We have no data of stage IV.) TTP was calculated on 72 patients including 57 patients with R+ resection and 15 with partial response or stable disease after radiotherapy. The 5-year time-to-progression (TTP) rates were 33% (41%, 24% in stage III and IV, respectively). Multivariate analysis showed that prognostic factors for OS were the Masaoka stage and adjuvant radiation for patients with stage III and IV. The Masaoka stage and resection margin after surgery had significant effects on FFR and TTP. Conclusion The type B3 thymoma often presented with the later stages at the diagnosis. The Masaoka stage was closely associated with OS, FFR, and TTP. Resection margin after surgery was related to TTP. Adjuvant radiotherapy may be beneficial to stage III and IV patients in this clinical setting.

This study utilizes information sciences (i.e., neural networks and exten sions) to reduce the burden for investigation of social sciences. Without loss of generality, the visual realism of pictures is utilized as the example to illustrate the proposed research flow chart. Pictures of web pages are important media for conveying meanings of information systems. Visual realism of pictures means the degree of similarity between pictures and real objects, and is an important topic in designing contents of information systems. In this paper, the neural network and its extension of derivative are applied to participants' preference for visual realism on web pages. This study includes three parts. In the first part, the participants' preferenc e for visual realism on web pages is experimentally investigated. The investigation results are recorded, analyzed and discussed. In the second part, we utilize the neural network to model and predict the investigation results of the first part. With the help of neural networks, o ne can model and predict the full investigated results from only part of the investigated information. In the third part, we develop a neu ral-network extension of derivative to predict the increasing or decreasing trends of investigation data. With the help of neural-network extension of derivative, the trends of investigation data can be predicted without plotting the overall data curves. It should be noted tha t the neural network and its extension of derivative share the same training procedures. No additional training work is required in the neural-network extension of derivative. The use of neural network and its extension of derivative will greatly reduce the investigation efforts and one can obtain almost the same results as full investigation. This study will be helpful in understanding, modeling and predicting participants' preference for contents of information systems. Although only specific examples are illustrated in this study, the pro posed research flow chart can be applied to many other problems of questionnaire investigation in social sciences.