Monkeypox virus infection of human astrocytes causes gasdermin B cleavage and pyroptosis.

Monkeypox virus (MPXV) infections in humans cause neurological disorders while studies of MPXV-infected animals indicate that the virus penetrates the brain. Pyroptosis is an inflammatory type of regulated cell death, resulting from plasma membrane rupture (PMR) due to oligomerization of cleaved gasdermins to cause membrane pore formation. Herein, we investigated the human neural cell tropism of MPXV compared to another orthopoxvirus, vaccinia virus (VACV), as well as its effects on immune responses and cell death. Astrocytes were most permissive to MPXV (and VACV) infections, followed by microglia and oligodendrocytes, with minimal infection of neurons based on plaque assays. Aberrant morphological changes were evident in MPXV-infected astrocytes that were accompanied with viral protein (I3) immunolabelling and detection of over 125 MPXV-encoded proteins in cell lysates by mass spectrometry. MPXV- and VACV-infected astrocytes showed increased expression of immune gene transcripts (IL12, IRF3, IL1B, TNFA, CASP1, and GSDMB). However, MPXV infection of astrocytes specifically induced proteolytic cleavage of gasdermin B (GSDMB) (50 kDa), evident by the appearance of cleaved N-terminal-GSDMB (30 kDa) and C-terminal- GSDMB (18 kDa) fragments. GSDMB cleavage was associated with release of lactate dehydrogenase and increased cellular nucleic acid staining, indicative of PMR. Pre-treatment with dimethyl fumarate reduced cleavage of GSDMB and associated PMR in MPXV-infected astrocytes. Human astrocytes support productive MPXV infection, resulting in inflammatory gene induction with accompanying GSDMB-mediated pyroptosis. These findings clarify the recently recognized neuropathogenic effects of MPXV in humans while also offering potential therapeutic options.

Comparison of contrast-enhanced ultrasonography and MRI results obtained by expert and novice radiologists indicating short-term response after transarterial chemoembolisation for hepatocellular carcinoma.

AIM: To evaluate inter-reader agreement between novice and expert radiologists in assessing contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI) images for detecting viable tumours with different sizes after conventional transarterial chemoembolisation (cTACE). MATERIALS AND METHODS: This prospective study included patients who had less than five hepatomas and who underwent cTACE. Hepatomas with one or two feeding arteries were selected as target lesions. CEUS and MRI were performed within 1 week after cTACE to evaluate viable tumours. RESULTS: The expert group had higher kappa values in evaluating all tumour sizes via CEUS compared with MRI. The novice group had similar kappa values. In patients with tumours measuring ≤3 cm, the expert group had higher kappa values in reading CEUS compared with MRI images; however, in the novice group, the kappa value was lower in evaluating CEUS compared with MRI images. In patients with tumours measuring >3 cm, the expert and novice groups had good to excellent kappa values. The confidence level of the two groups in reading MRI images was high; however, the novice group had a lower confidence level. CONCLUSION: CEUS is a convenient, cost-effective, and easy to apply imaging tool that can help interventionists perform early detection of viable hepatocellular carcinoma post-TACE. It has a higher inter-rater agreement in interpreting CEUS images compared with MRI images among expert radiologists even when they are extremely familiar with post-cTACE MRI images. In novice radiologists, there may be a learning curve to achieve good consistency in CEUS interpretation.

Blood lipid profile, HbA1c, fasting glucose, and diabetes: a cohort study and a two-sample Mendelian randomization analysis.

PURPOSE: The prevalence of diabetes is increasing worldwide. The associations between the lipid profile and glycated hemoglobin (HbA1c), fasting glucose, and diabetes remain unclear, so we aimed to perform a cohort study and a two-sample Mendelian randomization (MR) study to investigate the causality between blood lipid profile and HbA1c, fasting glucose, and diabetes. METHODS: A total of 25,171 participants from the Taiwan Biobank were enrolled. We applied a cohort study and an MR study to assess the association between blood lipid profile and HbA1c, fasting glucose, and diabetes. The summary statistics were obtained from the Asian Genetic Epidemiology Network (AGEN), and the estimates between the instrumental variables (IVs) and outcomes were calculated using the inverse-variance weighted (IVW) method. A series of sensitivity analyses were performed. RESULTS: In the cohort study, high-density lipoprotein cholesterol (HDL-C) was negatively associated with HbA1c, fasting glucose, and diabetes, while the causal associations between HDL-C and HbA1c (ßIVW = - 0.098, p = 0.003) and diabetes (ßIVW = - 0.594, p < 0.001) were also observed. Furthermore, there was no pleiotropy effect in this study using the MR-Egger intercept test and MR-PRESSO global test. CONCLUSIONS: Our results support the hypothesis that a genetically determined increase in HDL-C is causally related to a reduction in HbA1c and a lower risk of diabetes.

Effect of Taiwan's Diabetes Shared Care Program on the risk of periprosthetic joint infection after total joint arthroplasty in patients with type 2 diabetes mellitus: an eight-year population-based study.

BACKGROUND: Periprosthetic joint infection (PJI) is a significant post-arthroplasty complication for diabetic patients, with uncontrolled diabetes identified as a PJI risk factor. Taiwan's Diabetes Shared Care Program (DSCP) was established for holistic diabetes care. AIM: To evaluate the DSCP's impact on PJI incidence and patients' medical costs. METHODS: Data were analysed from Taiwan's National Health Insurance Research Database from 2010 to 2020, focusing on type 2 diabetes mellitus (DM) patients who had undergone arthroplasty. The study group involved DSCP participants, while a comparison group comprised non-participants with matched propensity scores for age, sex, and comorbidities. The primary outcome was the PJI incidence difference between the groups; the secondary outcome was the medical expense difference. FINDINGS: The study group consisted of 11,908 type 2 DM patients who had arthroplasty and joined the DSCP; PJI occurred in 128 patients. Among non-participants, 184 patients had PJI. The PJI incidence difference between the groups was statistically significant (1.07% vs 1.55%). The study group's medical costs were notably lower, regardless of PJI incidence. Multivariate regression showed higher PJI risk in patients in comparison group, aged >70 years, male, or who had obesity, anaemia. CONCLUSION: The study indicates that DSCP involvement reduces PJI risks and decreases annual medical costs for diabetic patients after arthroplasty. Consequently, the DSCP is a recommendable option for such patients who are preparing for total joint arthroplasty.

Untangling the Complex Interplay between Social Isolation, Anorexia, Sarcopenia, and Mortality: Insights from a Longitudinal Study.

BACKGROUND: Social isolation is a pervasive and debilitating condition that has adverse prognostic impacts. This condition often co-occurs with other geriatric syndromes, further exacerbating negative health outcomes. Given these considerations, the present study aims to elucidate the roles of social isolation in older adults with anorexia of aging and/or sarcopenia with respect to long-term mortality using a nationally representative cohort study. METHODS: Data were obtained from the Taiwan Longitudinal Study on Aging (TLSA), with a sample size of 3,762 study participants aged 50 years and older. Data from 1999 (wave 4) to 2015 (wave 9) were analyzed. The TLSA questionnaire was used to define social isolation, anorexia, and sarcopenia. Logistic regressions were employed to explore the associations between social isolation, anorexia, and sarcopenia. The Cox proportional hazard model was utilized to examine the synergistic effects of social isolation and anorexia or sarcopenia on 16-year all-cause mortality. RESULTS: After controlling for demographic information and comorbidities, older adults with social isolation were significantly associated with anorexia (adjusted odds ratio [aOR] 1.46 [95% confidence interval: 1.00-2.12, p=0.0475]) and sarcopenia (aOR 1.35 [95% CI: 1.12-1.64, p=0.0021]). Furthermore, the synergistic effects of social isolation with anorexia (aOR 1.65 [95% CI: 1.25-2.18, p=0.0004]) or sarcopenia (aOR 1.65 [95% CI: 1.42-1.92, p<0.0001]) were both significantly associated with higher risks of all-cause mortality, while social isolation alone revealed borderline statistical significance. CONCLUSIONS: Our findings indicate that social isolation is closely linked to anorexia and sarcopenia among middle-aged and older adults. Additionally, social isolation significantly exacerbates the long-term mortality risk associated with anorexia of aging and sarcopenia. However, social isolation alone appears to have borderline long-term mortality risk in this cohort. These findings underscore the importance of addressing social isolation in older adults with anorexia and/or sarcopenia to optimize their health outcomes and mitigate long-term mortality risk.

Subjective Cognitive Complaints: Comparing the Relation between Self-Reported Versus Informant-Reported Subjective Cognitive Complaints and Cognitive Performances in Cognitively Unimpaired, Mild Cognitive Impairment and Populations with Dementia.

BACKGROUND: Subjective cognitive decline is proposed to be associated with future mild cognitive impairment and dementia. A better understanding of the roles of self-reported and informant-reported subjective cognitive complaints can provide a more delicate picture in dementia recognition and early diagnosis. OBJECTIVES: To evaluate the accuracy of self-reported and informant-reported subjective cognitive complaints and the relation of subjective cognitive complaints and neuropsychological function in cognitively unimpaired, mild cognitive impairment and populations with dementia. DESIGN: We conducted a cross-sectional survey and evaluate the relations between subjective cognitive complaint scores and cognitive function in the different diagnostic groups. SETTING: We recruited individuals diagnosed with cognitively unimpaired or mild cognitive impairment or dementia with Alzheimer's clinical syndrome from a memory clinic in a tertiary medical center in Taiwan. PARTICIPANTS: Participants, age greater than 50 years old, were enrolled in this study. Participants' informants were also enrolled for the cognitive questionnaire assessment. MEASUREMENTS: Participants' and informants' subjective cognitive complaint scores were collected based on a 12-item questionnaire. Neuropsychological assessments of global cognitive function, memory, language, executive function, visuospatial function and calculation were performed. The relations between subjective cognitive complaint scores and cognitive function in the different diagnostic groups were assessed by linear regression model. RESULTS: There were 1536 individuals and 1028 informants enrolled in this study. Self-reported subjective cognitive complaint scores from early and late mild cognitive impairment and dementia with Alzheimer's clinical syndrome participants showed no significant differences, but informants' subjective cognitive complaint scores showed a significant increase. Informant-reported subjective cognitive complaint scores related to neuropsychological tests in population with dementia. Neither self-reported nor informant-reported subjective cognitive complaint scores related to neuropsychological tests in cognitively unimpaired and mild cognitive impairment populations. CONCLUSIONS: Self-reported subjective cognitive complaints alone may not be sufficient to demonstrate clinical significance in different stages of cognitive impairment. Incorporating informant-reported subjective cognitive complaints, along with considering individual's anxiety and depressive status, are crucial in assessing cognitive statuses in clinical practice.

Predictive Utility of Plasma Amyloid and Tau for Cognitive Decline in Cognitively Normal Adults.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease affecting mostly elderly adults. Recent diagnostic criteria for AD recommend the use of imaging and/or cerebrospinal fluid (CSF) biomarkers together with clinical presentation for a more persuasive diagnosis. The invasiveness and expense of such examinations have led to the search for blood-based biomarkers. The plasma levels of amyloid-ß (Aß) protein and tau peptides have been found to correlate with CSF levels and imaging findings in patients with AD. This study was conducted to explore the predictive utility of plasma Aß1-42 and total tau (t-tau) levels for cognitive decline in healthy adults. METHODS: In this prospective longitudinal study, we enrolled adults aged ≥ 50 years with normal cognition at Taipei Veterans General Hospital from November 2016 to April 2019. Blood samples were collected on recruitment, and plasma Aß1-42 and t-tau levels were quantified through immunomagnetic reduction. Thorough neurophysiological assessment was performed at baseline and at the annual follow-up visit. The participants were divided into two groups according to cognitive decline. The predictive utility of Aß1-42 and t-tau levels was evaluated by receiver operating characteristic curve analysis. RESULTS: Of 60 participants recruited, seven participants progressed to mild cognitive impairment and 53 retained normal cognition on follow-up (average 1.07 ± 0.2 years). The baseline levels of plasma biomarkers (Aß1-42, t-tau, and Aß1-42 × t-tau) were significantly higher in the progressive than in the stable group (p = 0.005, p = 0.007, and p = 0.005, respectively). Higher plasma biomarker levels (Aß1-42 ≥ 16.96 pg/ml and Aß1-42 × t-tau ≥ 382 pg2/ml2) predicted more cognitive decline on annual follow-up visits. CONCLUSION: Plasma Aß1-42 and t-tau levels have predictive utility for cognitive decline, even in subjects with normal cognition. Higher baseline plasma Aß1-42 and t-tau levels may indicate a higher risk of cognitive decline in cognitively normal adults.

[The optimal examination duration for the detection of epileptiform discharge in outpatient video-electroencephalography].

Objective: To determine the optimal examination duration by evaluating the detection rate of epileptiform discharges (EDs) with different examination duration of video-electroencephalography (EEG) in outpatients. Methods: Patients with EDs who underwent 4-hour EEG examination from Xuanwu Hospital, Capital Medical University from October 2020 to November 2021 were retrospectively enrolled, and the detection rates of EDs were calculated with examination duration of 0-0.5 h, 0-1 h, 0-2 h, 0-3 h, and 0-4 h (group A, B, C, D and E), respectively. For each patient, EDs in each hour (group H1, group H2, group H3, group H4) were counted, and the standardized amount of EDs was calculated. For each patient, EDs in wakefulness, drowsiness, non-rapid eye movement-Ⅰ (NREM-Ⅰ), NREM-Ⅱ and NREM-Ⅲ were counted, and the standardized amount of EDs in each state was calculated. Meanwhile, the sleep duration per hour of each patient was also counted (group H1', group H2', group H3', group H4'). The Wilcoxon paired test was used for intergroup comparison to determine the optimal examination duration. Results: A total of 80 patients were enrolled, and aged [M(Q1, Q3)]31 (21, 39) years (range: 5-68 years). There were 38 males and 42 females. The detection rate of EDs was 42.5% (34/80) in group A, 81.3% (65/80) in group B, and 100.0% (80/80) in group C, group D and group E, respectively. The standardized amount of EDs of H1, H2, H3 and H4 was 24.8% (7.8%, 44.2%), 41.5% (25.9%, 63.3%), 15.1% (1.3%, 27.8%) and 1.3% (0, 14.5%), respectively. The standardized amount of EDs of H2 was significantly higher than that of H1, H3 and H4 (all P<0.05). The standardized amount of EDs in wakefulness, drowsiness, NREM-Ⅰ, NREM-Ⅱ and NREM-Ⅲ were 9.6% (0, 28.2%), 3.6% (0, 16.9%), 3.3% (0, 11.8%), 47.3% (21.9%, 72.5%) and 0 (0, 11.5%), respectively. The standardized amount of EDs in NREM-Ⅱ was significantly higher than that in wakefulness, drowsiness, NREM-Ⅰ and NREM-Ⅲ (all P<0.05). The sleep duration in the group of the H1', H2', H3' and H4' was 13.6 (2.5, 23.6), 35.8 (16.5, 54.2), 14.5(0, 34.7) and 0 (0, 14.6) minutes, respectively. The sleep duration in the group of the H2' group was significantly longer than that in the group of H1', H3' and H4' (all P<0.05). Conclusion: The study recommends 2 hours video-EEG in outpatients, which not only ensures the detection rate of EDs, but also facilitates patient cooperation and optimizes the allocation of medical resources.

A two-ward acute care hospital outbreak of SARS-CoV-2 delta variant including a point-source outbreak associated with the use of a mobile vital signs cart and sub-optimal doffing of personal protective equipment.

BACKGROUND: The arrival of the Delta variant of SARS-CoV-2 was associated with increased transmissibility and illness of greater severity. Reports of nosocomial outbreaks of Delta variant COVID-19 in acute care hospitals have been described but control measures varied widely. AIM: Epidemiological investigation of a linked two-ward COVID-19 Delta variant outbreak was conducted to elucidate its source, risk factors, and control measures. METHODS: Investigations included epidemiologic analysis, detailed case review serial SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) testing of patients and healthcare workers (HCWs), viral culture, environmental swabbing, HCW-unaware personal protective equipment (PPE) audits, ventilation assessments, and the use of whole genome sequencing (WGS). FINDINGS: This linked two-ward outbreak resulted in 17 patient and 12 HCW cases, despite an 83% vaccination rate. In this setting, suboptimal adherence and compliance to PPE protocols, suboptimal hand hygiene, multi-bedded rooms, and a contaminated vital signs cart with potential fomite or spread via the hands of HCWs were identified as significant risk factors for nosocomial COVID-19 infection. Sudden onset of symptoms, within 72 h, was observed in 79% of all Ward 2 patients, and 93% of all cases (patients and HCWs) on Ward 2 occurred within one incubation period, consistent with a point-source outbreak. RT-PCR assays showed low cycle threshold (CT) values, indicating high viral load from environmental swabs including the vital signs cart. WGS results with ≤3 SNP differences between specimens were observed. CONCLUSION: Outbreaks on both wards settled rapidly, within 3 weeks, using a `back-to-basics' approach without extraordinary measures or changes to standard PPE requirements. Strict adherence to recommended PPE, hand hygiene, education, co-operation from HCWs, including testing and interviews, and additional measures such as limiting movement of patients and staff temporarily were all deemed to have contributed to prompt resolution of the outbreak.

Microstructural Evolution and an Improved Dynamic Recrystallization Kinetic Model of a Ni-Cr-Mo Alloy in Hot Deformation.

Microstructural evolution and dynamic recrystallization (DRX) behaviors of a Ni-Cr-Mo alloy were researched utilizing hot compressive experiments. The changed features of dislocation, subgrain and grain structure correlating to forming parameters were examined by transmission electron microscope (TEM) and electron backscatter diffraction (EBSD). Results illustrate that the consumption of dislocation and the coarsening of substructure/DRX grain are prominently enhanced with an increased forming temperature. However, the annihilation/interaction of dislocation and the expansion of subgrain/DRX grain boundary can be limited at a larger strain rate. Meanwhile, considering the discrepancy in DRX variation rates concerning the strain rate's ranges, an improved DRX kinetic model was developed. Compared to the classical DRX kinetic model, the good consistency between the forecasted and tested results demonstrates that the established improved DRX kinetic model can precisely characterize the DRX features of the Ni-Cr-Mo alloy over a wide strain rate range. Additionally, the EBSD's quantitative statistical results proved that the variation of DRX grain size can be supremely defined as the power formulation of the forming temperature and strain rate.

Highly Efficient Ag3PO4/g-C3N4 Z-Scheme Photocatalyst for Its Enhanced Photocatalytic Performance in Degradation of Rhodamine B and Phenol.

Ag3PO4/g-C3N4 heterojunctions, with different g-C3N4 dosages, were synthesized using an in situ deposition method, and the photocatalytic performance of g-C3N4/Ag3PO4 heterojunctions was studied under simulated sunlight conditions. The results revealed that Ag3PO4/g-C3N4 exhibited excellent photocatalytic degradation activity for rhodamine B (Rh B) and phenol under the same light conditions. When the dosage of g-C3N4 was 30%, the degradation rate of Rh B at 9 min and phenol at 30 min was found to be 99.4% and 97.3%, respectively. After five cycles of the degradation experiment for Rh B, g-C3N4/Ag3PO4 still demonstrated stable photodegradation characteristics. The significant improvement in the photocatalytic activity and stability of g-C3N4/Ag3PO4 was attributed to the rapid charge separation between g-C3N4 and Ag3PO4 during the Z-scheme charge transfer and recombination process.

The combination of soluble tumor necrosis factor receptor type 1 and fibroblast growth factor 21 exhibits better prediction of renal outcomes in patients with type 2 diabetes mellitus.

PURPOSE: Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD. METHODS: A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m2. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period. RESULTS: Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration [HR] 2.76, 95% confidence interval [CI] 1.36-5.60, p = 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03-3.69, p = 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86-10.65, p = 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria. CONCLUSION: Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.

[Neoadjuvant chemoradiotherapy combined with surgery versus direct surgery in the treatment of Siewert type II and III adenocarcinomas of the esophagogastric junction: long-term prognostic analysis of a prospective randomized controlled trial].

Objective: To investigate the effectiveness, safety, and prognosis of neoadjuvant chemoradiotherapy (nCRT) for Siewert type II and III adenocarcinomas of the esophagogastric junction (AEG). Methods: This study is a prospective randomized controlled clinical study (NCT01962246). AEG patients who were treated at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University from February 2012 to June 2016 were included. All of the enrolled patients were diagnosed with type II or III locally advanced AEG gastric cancer (T2-4N0-3M0 or T1N1-3M0) by gastroscopy and CT before operation; the longitudinal axis of the lesion was ≤ 8 cm; no anti-tumor treatment was previously given and no contraindications of chemotherapy and surgery were found. Case exclusion criteria: serious diseases accompanied by liver and kidney, cardiovascular system and other vital organs; allergy to capecitabine or oxaliplatin drugs or excipients; receiving any form of chemotherapy or other research drugs; pregnant or lactating women; patients with diseases resulting in difficulty to take capecitabine or with concurrent tumors. Based on sample size estimation, a total of 150 AEG patients were enrolled. Using the random number table method, the enrolled patients were divided into the nCRT group and the direct operation group with 75 cases in each group. The nCRT group received XELOX chemotherapy (capecitabine+ oxaliplatin) before surgery and concurrent radiotherapy (45 Gy, 25 times, 1.8 Gy/d, 5 times/week). Clinical efficacy of the nCRT group was evaluated by the solid tumor efficacy evaluation standard (RECIST1.1) and the tumor volume reduction rate was measured on CT. After completing the preoperative examination in the direct operation group, and 8-10 weeks after the end of nCRT in the nCRT group, surgery was performed. Laparoscopic exploration was initially performed. According to the Japanese "Regulations for the Treatment of Gastric Cancer", a transabdominal radical total gastrectomy combined with perigastric lymph node dissection was performed. The primary outcome was the 3-year overall survival (OS) and disease-free survival rate (DFS); the secondary outcomes were R0 resection rate, the toxicity of chemotherapy, and surgical complications. The follow-up ended on December 31, 2019. The postoperative recurrence, metastasis and survival time of the two groups were collected. Results: After excluding patients with incomplete clinical data, patients or family members requesting to withdraw informed consent, and those failing to follow the treatment plan, 63 cases in the nCRT group and 69 cases in the direct operation group were finally enrolled in the study. There were no statistically significant differences in baseline characteristics of the two groups (all P>0.05). Sixty-three patients in the nCRT group were evaluated by RECIST1.1 after treatment, the image based effective rate was 42.9% (27/63), and the stable disease rate was 98.4% (62/63); the tumor volume before and after nCRT measured on CT was (58.8±24.4) cm(3) and (46.6±25.7) cm(3), respectively, the effective rate of tumor volume reduction measured by CT was 47.6% (30/63). Incidences of neutrophilopenia [65.1% (41/63) vs. 40.6% (28/69), χ(2)=7.923, P=0.005], nausea [81.0% (51/63) vs. 56.5% (39/69), χ(2)=9.060, P=0.003] and fatigue [74.6% (47/63) vs. 42.0% (29/69), χ(2)=14.306, P=0.001] in the nCRT group were significantly higher than those in the direct surgery group. Radiation gastritis/esophagitis and radiation pneumonia were unique adverse reactions in the nCRT group, with incidences of 52.4% (33/63) and 15.9%(10/63), respectively. The classification of tumor regression of 63 patients in nCRT group presented as 11 cases of grade 0 (17.5%), 20 cases of grade 1 (31.7%), 28 cases of grade 2 (44.4%), and 5 cases of grade 3 (7.9%). Eleven (17.5%) patients achieved pathologic complete response. Sixty-one (96.8%) patients in the nCRT group underwent R0 resection, which was higher than 87.0% (60/69) in the direct surgery group (χ(2)=4.199, P=0.040). The mean number of harvested lymph nodes in the specimens in the nCRT group and the direct operation group was 27.6±12.4 and 26.8±14.6, respectively, and the difference was not statistically significant (t=-0.015, P=0.976). The pathological lymph node metastasis rate and lymph node ratio in the two groups were 44.4% (28/63) vs. 76.8% (53/69), and 4.0% (70/1 739) vs. 21.9% (404/1 847), respectively with statistically significant differences (χ(2)=14.552, P<0.001, and χ(2)=248.736, P<0.001, respectively). During a median follow-up of 52 (27-77) months, the 3-year DFS rate in the nCRT group and the direct surgery group was 52.4% and 39.1% (P=0.049), and the 3-year OS rate was 63.4% and 52.2% (P=0.019), respectively. According to whether the tumor volume reduction rate measured by CT was ≥ 12.5%, 63 patients in the nCRT group were divided into the effective group (n=30) and the ineffective group (n=33). The 3-year DFS rate of these two subgracps was 56.6% and 45.5%, respectively without significant difference (P=0.098). The 3-year OS rate was 73.3% and 51.5%,respectively with significant difference (P=0.038). The 3-year DFS rate of patients with the tumor regression grades 0, 1, 2 and 3 was 81.8%, 70.0%, 44.4%, and 20.0%, repectively (P=0.024); the 3-year OS rate was 81.8%, 75.0%, 48.1% and 40.0%, repectively (P=0.048). Conclusion: nCRT improves treatment efficacy of Siewert type II and III AEG patients, and the long-term prognosis is good.

Addition of dexamethasone to manage acute phase responses following initial zoledronic acid infusion.

Acute phase response (APR), including myalgia, influenza-like symptoms, headache, arthralgia, and pyrexia, is the most common adverse reaction to initial zoledronic acid infusion. Dexamethasone plus acetaminophen is effective in significantly reducing the incidence and severity of APR. INTRODUCTION: Acute phase response (APR), including myalgia, influenza-like symptoms, headache, arthralgia, and pyrexia, is due to immunomodulatory actions and is the most common adverse reaction to zoledronic acid (ZOL). The aims of our study were to compare the differences between acetaminophen and dexamethasone plus acetaminophen on the incidence and severity of APRs and to clarify the clinical factors related to APR with initial ZOL infusion. METHODS: Patients with osteoporosis receiving their first ZOL infusion (N = 96) were assigned into two groups and given either acetaminophen (58 patients, control group) or acetaminophen plus dexamethasone (38 patients, study group). APRs were assessed through telephone interviews 2 weeks later post-infusion. Clinical, demographic, and serologic data were recorded. RESULTS: There was a significant increase in the incidence and severity of any APR in the control group than the study group (67% vs. 34%, p = 0.003; 0.69 ± 0.50 vs. 0.34 ± 0.48, p = 0.001). Among the APRs, only myalgia incidence and score were significantly higher in the control group than in the study group. Multivariate analysis demonstrated that previous use of osteoporosis medication and participation in the study group was negatively related to the occurrence of any APR or myalgia. Advanced age was shown to significantly increase myalgia. Study group participants had significantly reduced severity of myalgia. The adherence for redosing ZOL was significantly higher in the study group. CONCLUSION: Dexamethasone plus acetaminophen is effective in significantly reducing the incidence and severity of APR, especially myalgia, and increasing adherence following initial ZOL infusion.

Au nanostar nanoparticle as a bio-imaging agent and its detection and visualization in biosystems.

In the present work, we report the imaging of Au nanostars nanoparticles (AuNSt) and their multifunctional applications in biomedical research and theranostics applications. Their optical and spectroscopic properties are considered for the multimodal imaging purpose. The AuNSt are prepared by the seed-meditated method and characterized for use as an agent for bio-imaging. To demonstrate imaging with AuNSt, penetration and localization in different biological models such as cancer cell culture (A549 lung carcinoma cell), 3D tissue model (multicellular tumor spheroid on the base of human oral squamous carcinoma cell, SAS) and murine skin tissue are studied. AuNSt were visualized using fluorescence lifetime imaging (FLIM) at two-photon excitation with a pulse duration 140 fs, repetition rate 80 MHz and 780 nm wavelength femtosecond laser. Strong emission of AuNSt at two-photon excitation in the near infrared range and fluorescence lifetime less than 0.5 ns were observed. It allows using AuNSt as a fluorescent marker at two-photon fluorescence microscopy and lifetime imaging (FLIM). It was shown that AuNSt can be observed inside a thick sample (tissue and its model). This is the first demonstration using AuNSt as an imaging agent for FLIM at two-photon excitation in biosystems. Increased scattering of near-infrared light upon excitation of AuNSt surface plasmon oscillation was also observed and rendered using a possible contrast agent for optical coherence tomography (OCT). AuNSt detection in a biological system using FLIM is compared with OCT on the model of AuNSt penetrating into animal skin. The AuNSt application for multimodal imaging is discussed.

LncRNA SNHG6 can regulate the proliferation and apoptosis of rat degenerate nucleus pulposus cells via regulating the expression of miR-101-3p.

OBJECTIVE: Intervertebral disc (IVD) degeneration (IDD) is a well-known consequence of low back pain, as characterized by aberrant cell proliferation and apoptosis of nucleus pulposus (NP) cells. In the present study, we aimed to investigate the effect of lncRNA small nucleolar RNA host gene 6 (SNHG6) on deregulated functions of degenerative NP cells. MATERIALS AND METHODS: After the establishment of rat IDD models, the mRNA and protein levels of collagen-I (Col-I) and collagen II (Col-II), and mRNA level of SNHG6 were detected by using reverse transcription quantitative Real Time-PCR (RT-qPCR) and Western blot. We further investigated the role and molecular mechanisms of SNHG6 by overexpressing or silencing it in degenerative NP cells. Cell proliferation was measured by MTT assay and EdU staning, and apoptosis was measured by flow cytometry. The target of SNHG6 was identified by starBase and Dual-Luciferase reporter assay. RESULTS: Upregulation of SNHG6 was found in IDD NP cells than in normal cells, associated with higher level of Col-I and lower level of Col-II. Overexpression of SNHG6 inhibited cell proliferation and enhanced apoptosis, accompanied by increased expression of Bax, caspase-3, and p21, as well as decreased expression of Bcl-2, which was in reverse to the treatment of SNHG6 silencing. Moreover, miR-101-3p was indicated as a target of SNHG6, and inhibition of miR-101-3p reversed the effects on proliferation and apoptosis induced by SNHG6. CONCLUSIONS: SNHG6 suppressed cell proliferation and induced apoptosis by increasing expression of Bax, caspase-3, p21 and decreasing Bcl-2 through targeting miR-101-3p, which suggested that SNHG6 could be a potential target in the treatment of IDD.

Tunable light absorption of graphene using topological interface states.

A tunable light absorption of graphene using topological interface states (TISs) is presented. The monolayer graphene is embedded in the interface of asymmetric topological photonic crystals (ATPCs). A strong absorption phenomenon occurs by the excitation of TISs. It is found that the absorption spectra are intensively dependent on the chemical potential of graphene and the periodic number of the ATPCs. Furthermore, the absorption can be rapidly switched in a slight variation of chemical potential, which is modulated by the applied gate voltage on graphene. This study not only opens up a new approach for enhancing light-monolayer graphene interactions, but also provides for practical applications in high absorption optoelectronic devices. This strong absorption phenomenon is different from those in Fabry-Perot resonators, nano-cavities photonic crystal, and traditional topological photonic crystals (TPCs).

Deformation Behavior and Precipitation Features in a Stretched Al-Cu Alloy at Intermediate Temperatures.

Deformation behavior and precipitation features of an Al-Cu alloy are investigated using uniaxial tensile tests at intermediate temperatures. It is found that the true stress drops with the decreased strain rate or the increased deformation temperature. The number of substructures and the degree of grain elongation decrease with the raised temperature or the decreased strain rate. At high temperatures or low strain rates, some dynamic recrystallized grains can be found. The type of precipitates is influenced by the heating process before hot tensile deformation. The content and size of precipitates increase during tensile deformation at intermediate temperatures. As the temperature increases over 200 °C, the precipitation process (Guinier Preston zone (G.P. zones)→θ'' phase→θ' phase) is enhanced, resulting in increased contents of θ'' and θ' phases. However, θ'' and θ' phases prefer to precipitate along the {020}Al direction, resulting in an uneven distribution of phases. Considering the flow softening degree and the excessive heterogeneous precipitation of θ'' and θ' phases during hot deformation, the reasonable strain rate and temperature are about 0.0003 s-1 and 150 °C, respectively.

Gallium Nitride (GaN) High-Electron-Mobility Transistors with Thick Copper Metallization Featuring a Power Density of 8.2 W/mm for Ka-Band Applications.

Copper-metallized gallium nitride (GaN) high-electron-mobility transistors (HEMTs) using a Ti/Pt/Ti diffusion barrier layer are fabricated and characterized for Ka-band applications. With a thick copper metallization layer of 6.8 µm adopted, the device exhibited a high output power density of 8.2 W/mm and a power-added efficiency (PAE) of 26% at 38 GHz. Such superior performance is mainly attributed to the substantial reduction of the source and drain resistance of the device. In addition to improvement in the Radio Frequency (RF) performance, the successful integration of the thick copper metallization in the device technology further reduces the manufacturing cost, making it extremely promising for future fifth-generation mobile communication system applications at millimeter-wave frequencies.

Cytoplasmic factories, virus assembly, and DNA replication kinetics collectively constrain the formation of poxvirus recombinants.

Poxviruses replicate in cytoplasmic structures called factories and each factory begins as a single infecting particle. Sixty-years ago Cairns predicted that this might have effects on vaccinia virus (VACV) recombination because the factories would have to collide and mix their contents to permit recombination. We've since shown that factories collide irregularly and that even then the viroplasm mixes poorly. We've also observed that while intragenic recombination occurs frequently early in infection, intergenic recombination is less efficient and happens late in infection. Something inhibits factory fusion and viroplasm mixing but what is unclear. To study this, we've used optical and electron microscopy to track factory movement in co-infected cells and correlate these observations with virus development and recombinant formation. While the technical complexity of the experiments limited the number of cells that are amenable to extensive statistical analysis, these studies do show that intergenic recombination coincides with virion assembly and when VACV replication has declined to ≤10% of earlier levels. Along the boundaries between colliding factories, one sees ER membrane remnants and other cell constituents like mitochondria. These collisions don't always cause factory fusion, but when factories do fuse, they still entrain cell constituents like mitochondria and ER-wrapped microtubules. However, these materials wouldn't seem to pose much of a further barrier to DNA mixing and so it's likely that the viroplasm also presents an omnipresent impediment to DNA mixing. Late packaging reactions might help to disrupt the viroplasm, but packaging would sequester the DNA just as the replication and recombination machinery goes into decline and further reduce recombinant yields. Many factors thus appear to conspire to limit recombination between co-infecting poxviruses.