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Recently, Far-infrared Light Emitting Diodes have attracted considerable interest in the research field worldwide. Emerging light therapy requires effective red/far-infrared light resources in clinical and plant photomorphogenesis to target or promote the interaction of light with living organisms. Here, Gd3Al4GaO12:Cr3+ (hereinafter referred to as: GAGG:Cr3+) phosphor was synthesized by high-temperature solid-phase method, and the crystal structure, morphology, and luminescence properties of this series of phosphor samples were studied. Through X-ray powder diffraction to obtain pure phase GAGG:Cr3+ series phosphor. Under the excitation of 420nm blue light, a broad band emission from 640 to 850nm is obtained, which is the result of the transition of Cr3+ 4T2→4A2 level. A sharp emission peak at 693nm is the R line belonging to Cr3+ in Gd3Al4GaO12 garnet. R line is assigned to the spin-forbidden 2E→4A2 transitions of Cr3+ ions that occupy the ideal octahedral sites. As the Cr3+ doping concentration increases, the luminous intensity of the sample increases first and then decreases. When the doping concentration of Cr3+ is 0.1mol phosphor,the luminous intensity is strongest at one single broad peak at about 712nm. At 440k, the R sharp line (693nm) and broad band (712nm) emission intensity maintained 78.6% and 71.8% , compared to room temperature intensity, respectively. The change of fluorescence lifetime at different temperatures gives the mechanism of fluorescence change with temperature. The current exploration will pave a promising way to engineer GAGG:Cr3+ activated optoelectronic devices for all kinds of photobiological applications.

BACKGROUND Foreign bodies stuck in the throat and esophagus can be discharged through the digestive tract. Esophageal-lodged foreign bodies can cause secondary injury or detrimental response, with hepatic abscess being one such, albeit rare, outcome. Review and discussion of the few case reports on such instances will help to improve the overall understanding of such conditions and aid in differential diagnosis to improve patient outcome. CASE SUMMARY A 51-year-old female patient with pre-existing diabetes visited our hospital following a 15-d experience of chills and fever. Both plain and enhanced magnetic resonance imaging and color Doppler ultrasound examination of the liver and gallbladder revealed a space-occupying lesion in the caudate lobe of the liver (7.8 cm × 6.0 cm × 5.0 cm). Initially, a malignant tumor was suspected, but differential diagnosis was unable to exclude the possibility of hepatic abscess. Conservative anti-infection therapy produced a less than ideal outcome. Additional examination by hepatobiliary imaging with computed tomography suggested a foreign body present in the upper abdomen and hepatic abscess, and subsequent endoscopy revealed a sinus tract in the anterior wall of the duodenal bulb. Therefore, surgery was performed to remove the object (fishbone) and drain the abscess. After a 2-wk uneventful recovery, the patient was discharged. The final diagnosis was foreign body-induced hepatic abscess of the caudate lobe. CONCLUSION Differential diagnosis is important for hepatic masses, and systematic examination and physician awareness can aid in diagnosing and curing such rare conditions.

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease caused by an abnormal response of the intestinal mucosal immune system, including ulcerative colitis and Crohn's disease. IBD is also accompanied by extraintestinal complications, such as joint, skin, and eye diseases. In recent years, phytomedicine has played an important role in the treatment of IBD because of its strong anti-inflammatory activities and minor side effects. Due to the lack of a review of the literature examining the extent to which phytomedicine can be used to treat IBD, this paper summarizes the experimental research on IBD from the perspective of phytomedicine according to the structural classification of phytomedicine and provides a reference for the further development of new IBD therapies.

Aim of this study was to evaluate the association between multiple essential microelements exposure and the aggressive clinicopathologic characteristics of papillary thyroid carcinoma (PTC). The concentrations of 10 essential microelements in urine [cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), strontium (Sr), zinc (Zn), and iodine (I)] were measured in 608 patients newly diagnosed with PTC, including 154 males and 454 females. Chi square test and Wilcoxon rank sum test were used to compare general characteristics among males and females. Multivariate logistic regression was used to evaluate the associations between essential microelements and PTC clinicopathologic characteristics in single- and multi-microelement models. In this study, we only observed that the frequency of lymph node metastasis in males was higher than in females, and males had higher levels of zinc than females, but males had lower levels of iodine than females. It was found that high levels of Fe were associated with decreased risk of PTC tumor size > 1 cm, capsular invasion, and advanced T stage (T3/4a/4b). High levels of Co and Mo were associated with decreased risk of capsular invasion and lymph node metastasis, respectively. However, high levels of Mn and Sr were associated with increased risk of capsular invasion and multifocality respectively, and both were associated with increased risk of advanced T stage (T3/4a/4b). These findings indicated that certain essential microelements might have potential effects on PTC progression and aggressiveness. Further studies are required to confirm these findings.

DNA methylation is an important epigenetic change in carcinogenesis. However, the function and mechanism of DNA methylation dysregulation in nasopharyngeal carcinoma (NPC) is still largely unclear. Our previous genome-wide microarray data showed that NFAT1 is one of the most hypermethylated transcription factor genes in NPC tissues. Here, we found that NFAT1 hypermethylation contributes to its down-regulation in NPC. NFAT1 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition in vitro and tumor metastasis in vivo. We further established that the tumor suppressor effect of NFAT1 is mediated by its inactivation of ITGA6 transcription. Our findings suggest the significance of activating NFAT1/ITGA6 signaling in aggressive NPC, defining a novel critical signaling mechanism that drives NPC invasion and metastasis and providing a novel target for future personalized therapy.

Background:. Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH. Methods:. Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0–3 months) and a follow-up phase (3–12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance). Results:. Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ± 2.3 mL and 4.1 ± 1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ± 1.8 cm and 5.1 ± 1.6 cm (P 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference. Conclusions:. The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research. Trial Registration:. ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.

Background:. Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity. Methods:. This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson's disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS). Results:. The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA. Conclusions:. Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.

Background Cystic fibrosis (CF) is a common, life-threatening genetic disease in Caucasians but rarely reported in Chinese population. The prevalence and population-specific genetic spectrum of CF in China needs to be systematically estimated and compared with Caucasians. Materials and methods We reviewed 30,951 exome-sequencing samples, including 20,909 pediatric patient samples and 10,042 parent samples, from Chinese Children's Rare Disease Genetic Testing Clinical Collaboration System (CCGT). After the in-lab filtration process, 477 candidate variants of CFTR gene were left and 53 variants were manually curated as pathogenic/likely-pathogenic (P/LP). These P/LP variants were adopted to estimate CF prevalence in three methods: the carrier frequency method, the permutation-combinations method and the Bayesian framework method. Allele frequencies of the 477 CFTR variants were compared with non-Finland European (NFE) and East Asian (EAS) from gnomAD database. To investigate the haplotype structure difference of CFTR, another 2067 whole-genome-sequencing samples from CCGT and 195 NFE from 1000 genome project were analyzed by Shapeit4 software. Result With the 53 manually curated P/LP variants in CFTR gene, we excluded individuals identified or suspected with CF and their parents in our cohorts and estimated the Chinese CF prevalence is approximately 1/128,434. Only 21 (39.6%) of the 53 variants were included in Caucasian specific CF screening panels, resulting in significantly under-estimation of CF prevalence in our children cohort (1/143,171 vs. 1/1,387,395, P = 5e−24) and parent’s cohort (1/110,127 vs. 1/872,437, P = 7e−10). The allele frequencies of six pathogenic variants (G970D, D979A, M469V, G622D, L88X, 1898+5G->T) were significantly higher in our cohorts compared with gnomAD-NFE population (all P-value Conclusions Chinese population showed significantly different genetic spectrum pattern in CFTR gene compared with Caucasian population, and thus a Chinese-specific CF screening panel is needed.

Tinea capitis comprising of tinea favosa and kerion is mostly seen in school-aged children. Some tinea capitis often presented with insignificant findings under the naked eyes are easily overlooked. The authors describe an unusual case of tinea capitis caused by Trichophyton violaceum. The patient was an 8-year-old girl, with a history of pruritus on the scalp for more than one year. A diagnosis of tinea capitis was confirmed by clinical examination aided by dermoscopy, calcium fluorescent microscopy and culture. Comma and corkscrew hairs are two specific dermoscopic patterns of tinea capitis. The patient was treated with systemic itraconazole, topical application with 1% naftifine 0.25% ketoconazole cream followed after daily hair wash with 2% ketoconazole shampoo for 8 weeks.

Background/Aims Pancreatic ductal adenocarcinoma (PDAC) is associated with high mortality, even after surgical resection. The existing predictive models for survival have limitations. This study aimed to develop better nomograms for predicting overall survival (OS) and cancer‐specific survival (CSS) in PDAC patients after surgery. Methods A total of 6323 PDAC patients were retrospectively recruited from the Surveillance, Epidemiology, and End Results (SEER) database and randomly allocated into training, validation, and test cohorts. Multivariate Cox regression analysis was conducted to identify significant independent factors for OS and CSS, which were used for construction of nomograms. The performance was evaluated, validated, and compared with that of the 8th edition AJCC staging system. Results Ten independent factors were significantly correlated with OS and CSS. The 1‐, 3‐, and 5‐year OS rates were 40%, 20%, and 15%, and 1‐, 3‐, and 5‐year CSS rates were 45%, 24%, and 19%, respectively. The nomograms were calibrated well, with c‐indexes of 0.640 for OS and 0.643 for CSS, respectively. Notably, relative to the 8th edition AJCC staging system, the nomograms were able to stratify each AJCC stage into three prognostic subgroups for more robust risk stratification. Furthermore, the nomograms achieved significant clinical validity, exhibiting wide threshold probabilities and high net benefit. Performance assessment also showed high predictive accuracy and reliability. Conclusions The predictive ability and reliability of the established nomograms have been validated, and therefore, these nomograms hold potential as novel approaches to predicting survival and assessing survival risks for PDAC patients after surgery., In the present study, we constructed and validated nomograms for predicting the 1‐, 3‐, and 5‐year OS and CSS rates after surgical resection of PDAC. The nomograms established in the present study showed good performance for the prediction of OS and CSS, which was superior to that of the existing, conventional AJCC staging system with an improved net benefit. Therefore, these nomograms hold promise as novel prognosis models for improving the prediction of individualized postoperative survival and improving the care of PDAC patients following surgical resection.

Candidal granuloma is a rare and refractory disease in clinical practice, usually reported in immunocompromised patients. We report a 57-year-old man who presented with candidal granuloma caused by Candida tropicalis. The diagnosis was confirmed according to histopathology and molecular identification. Prolonged duration of initial antifungal therapy did not obtain satisfactory improvement. Finally, the refractory disease was successfully treated by itraconazole and terbinafine in combination with hyperthermia and cryotherapy. The “blackish-red dot” dermoscopic sign of the verrucous granuloma gradually resolved during the treatment.

Aim and Objective: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common chronic kidney disease that leads to End-Stage Renal Disease (ESRD). The key target of this therapy is to prevent the progression of kidney failure. Tolvaptan could slow kidney cyst growth and are proven highly effective. The aims of this analysis are to perform a systematic review, estimate and evaluate the efficacy and safety of tolvaptan in ADPKD patients. Materials and Methods: Randomized controlled trials of tolvaptan in ADPKD were identified in PubMed, Ovid, Web of Science and the Cochrane Library electronic database. The changes observed in kidney function, treatment efficiency and the incidence of adverse events between the tolvaptan and placebo groups were compared. Data were analyzed by the RevMan software. Results: Eight trials, including 7 double-blinded randomised controlled trials and 1 quasi RCT involving 1,536 patients were extracted. Significant differences in the annual rate of change in the total kidney volume TKV at any stages of CKD (MD = -3.32, 95%CI =-4.57,-2.07, I2 =70%) and the glomerular filtration rate (MD = 1.4, 95%CI = 0.83,1.97, I2 =0%) were observed between the tolvaptan group and the placebo group. Subgroup analysis of patients in different CKD stages also showed the same conclusion. There was an increase in the urine osmolality, and 24-hour urine volume in patients receiving tolvaptan. Tolvaptan reduced the rate of serious hypertension and kidney pain events in ADPKD patients. At higher doses, it increased the rate of adverse events (liver injuries, thirst, pollakiuria, and nocturia). There was no significant risk of bias in the included studies. Conclusions: Tolvaptan has a beneficial effect on ADPKD, but is associated with an increase in adverse events at high doses when compared with the placebo. Further RCTs on tolvaptan may be required to support this conclusion.

Purpose – With the increasing uncertainty of China's domestic political and economic environment in recent years, Korean MNC subsidiaries in the Chinese market face greater challenges and competition. Based on the insufficiency of existing research and the need for enterprise management practices, this paper uses the Chinese subsidiaries of Korean MNCs as an example to study and explore how knowledge management and dynamic capabilities affect ambidextrous innovation and the relationship between ambidextrous innovation and subsidiary performance. Design/methodology – From January to March 2019, this study collected 341 valid questionnaires using a survey company specializing in China for the members of the Chinese subsidiaries of Korean MNCs to verify the hypotheses. Using the collected data, the study model was verified using the Smart PLS 3.0 statistical package. Findings – Knowledge transfer and knowledge sharing have positive effects on dynamic capabilities and ambidextrous innovation, and dynamic capabilities have a positive impact on ambidextrous innovation. Ambidextrous innovation has been shown to have a significant effect on subsidiary performance. In addition, a partial mediating effect of dynamic capabilities on the relationship between knowledge management and ambidexterity innovation was found. Originality/value – In the academic context, this paper contributes theoretically to the relationship between knowledge management and ambidextrous innovation, as well as the mechanism of dynamic capability, and to verify the relationship between ambidextrous innovation and corporate performance. Against the background of MNC management, the results of this study provide further enlightenment for managers of subsidiaries.

Background Quercetin (QUE) is a flavonol reported with anti-inflammatory and antioxidant activities, and previous results from the group of this study have demonstrated its neuroprotective effect against lipopolysaccharide-induced neuropsychiatric injuries. However, little is known about its potential effect on neuropsychiatric injuries induced or accompanied by metabolic dysfunction of glucose and lipids. Methods A nonalcoholic fatty liver disease (NAFLD) rat model was induced via a high-fat diet (HFD), and glucolipid parameters and liver function were measured. Behavioral performance was observed via the open field test (OFT) and the Morris water maze (MWM). The plasma levels of triggering receptor expressed on myeloid cells-1 (TREM1) and TREM2 were measured via enzyme-linked immunosorbent assay (ELISA). The protein expression levels of Synapsin-1 (Syn-1), Synaptatogmin-1 (Syt-1), TREM1 and TREM2 in the hippocampus were detected using western blotting. Morphological changes in the liver and hippocampus were detected by HE and Oil red or silver staining. Results Compared with the control rats, HFD-induced NAFLD model rats presented significant metabolic dysfunction, hepatocyte steatosis, and impaired learning and memory ability, as indicated by the increased plasma concentrations of total cholesterol (TC) and triglyceride (TG), the impaired glucose tolerance, the accumulated fat droplets and balloon-like changes in the liver, and the increased escaping latency but decreased duration in the target quadrant in the Morris water maze. All these changes were reversed in QUE-treated rats. Moreover, apart from improving the morphological injuries in the hippocampus, treatment with QUE could increase the decreased plasma concentration and hippocampal protein expression of TREM1 in NAFLD rats and increase the decreased expression of Syn-1 and Syt-1 in the hippocampus. Conclusions These results suggested the therapeutic potential of QUE against NAFLD-associated impairment of learning and memory, and the mechanism might involve regulating the metabolic dysfunction of glucose and lipids and balancing the protein expression of synaptic plasticity markers and TREM1/2 in the hippocampus.

An 85-years-old farmer presented with verrucous mass in the right lower leg inner side for five years, and then the left leg inner side gradually developed a similar lesion. Yeast cells were observed in the tissue with PAS and GMS. Sporothrix globose was identified by culture, ITS, and CAL. The patient improved after 4 months of oral terbinafine. The development and distribution of exceptional characteristics lesion indicated self-inoculation by the close touch of legs during sleeping resulted in symmetrical sporotrichosis.

A two-stage method for matching private idle parking slots with demanders is proposed based on the core idea of private idle parking slot sharing to solve the problem of parking difficulty ...

Infantile hemangioma is a common and challenging benign vascular tumor. Although involution is spontaneous, approximately 10% of infantile hemangioma of large size or in specific locations may cause ulceration, severe cosmetic and functional problems that may require intervention. Treatment options include oral propranolol, topical timolol, and oral corticosteroids. However, the clinical response is not always satisfactory. We report the case of a 4-month-old boy who presented with an irregular erythematous plaque on his left shoulder 3 days after birth. Infantile hemangioma was diagnosed. Topical application of 0.5 ml of 0.5% timolol maleate eye drops for half an hour each time three times a day was initiated. After nearly 3 months of follow-up, the size of the lesion gradually increased. Finally, after 115 days of treatment with itraconazole oral solution (the total dose was about 4025 mg), the refractory infantile hemangioma was successfully treated. Hepatic and renal function remained normal with only mild diarrhea during the course of oral medication. Treatment compliance of oral itraconazole in infants has been reported to be good. Dermoscopy and magnetic resonance imaging (MRI) played a crucial role in in vivo observation of the hemangioma changes with vascular regression during the treatment process.

Asthma is a common chronic inflammatory airway disorder associated with considerable morbidity, mortality and increased health care costs worldwide. Traditional Chinese medicine (TCM) as a functional food characterized by multi-compound and multi-target have been proven to be effective in treating asthma based on a holistic way. However, the potential molecular or systems mechanism of TCM to anti-asthma has not yet been fully elucidated. A systems pharmacology-based method combining the ADME evaluation, herb feature mapping, drug target fishing, network pharmacology, as well as pathway analysis is developed to comprehensively elucidate the potential therapeutic mechanism of asthma, exemplified by the anti-asthma herbal medicine intervention (ASHMI). Our study not only provides a comprehensive thinking for better understanding the complex action mechanism of ASHMI on asthma from a system level, but also proposed a rational novel way to facilitate the treatment of asthma.

B7-H3, one of the costimulatory members participating in checkpoint pathway, has been shown to be upregulated after hepatitis B virus (HBV) infection. To further explore the clinical significance of dynamic B7-H3 expression during the progression of HBV infection, we systematically investigated the expression pattern of B7-H3 and the correlation of B7-H3 expression with the ratio of T lymphocyte subsets and clinical parameters at different stages in the course of the disease. Flow cytometry and enzyme-linked immunosorbent assay data showed that soluble form of B7-H3 (sB7-H3) was positively correlated with the frequency of Treg cells in acute hepatitis B (AHB), chronic hepatitis B (CHB), and hepatocellular carcinoma patients with HBV infection (HBV-HCC). Membrane form of B7-H3 (mB7-H3) expressed on Treg cells and monocytes was positively correlated with the frequency of Treg cells in CHB. SB7-H3 had relationship with mB7-H3 expressed on Treg cells and monocytes at different stages during HBV infection, except for HBV-HCC. MB7-H3 expressed on Treg cells was positively correlated with that on monocytes in AHB, CHB, HBV-liver cirrhosis, and HBV-HCC. The B7-H3 expression was positively correlated with aspartate aminotransferase and alanine aminotransferase levels in CHB and sB7-H3 level was higher in late tumor/node/metastasis (TNM) stage in HCC. Higher mB7-H3 expression was associated with greater tumor size, later TNM stage, and worse prognosis in HBV-HCC indicated by immunohistochemistry. Taken together, these results suggested that B7-H3 might contribute to the progression of HBV infection by triggering inhibitory signals in effector T cells and it was closely associated with the progression and poor prognosis during HBV infection. B7-H3 could be utilized as a potential clinical indicator and a potential target for therapeutic strategies against HBV infection.

Systemic lupus erythematosus (SLE) is a typical autoimmune disease with a strong genetic disposition. Genetic studies have revealed that single-nucleotide polymorphisms (SNPs) in zinc finger protein (ZNF)-coding genes are associated with susceptibility to autoimmune diseases, including SLE. The objective of the current study was to evaluate the correlation between ZNF76 gene polymorphisms and SLE risk in Chinese populations. A total of 2801 individuals (1493 cases and 1308 controls) of Chinese Han origin were included in this two-stage genetic association study. The expression of ZNF76 was evaluated, and integrated bioinformatic analysis was also conducted. The results showed that 28 SNPs were associated with SLE susceptibility in the GWAS cohort, and the association of rs10947540 was successfully replicated in the independent replication cohort (Preplication = 1.60 × 10−2, OR 1.19, 95% CI 1.03–1.37). After meta-analysis, the association between rs10947540 and SLE was pronounced (Pmeta = 9.62 × 10−6, OR 1.29, 95% CI 1.15–1.44). Stratified analysis suggested that ZNF76 rs10947540 C carriers were more likely to develop relatively high levels of serum creatinine (Scr) than noncarriers (CC + CT vs. TT, p = 9.94 × 10−4). The bioinformatic analysis revealed that ZNF76 rs10947540 was annotated as an eQTL and that rs10947540 was correlated with decreased expression of ZNF76. Remarkably, significantly reduced expression of ZNF76 was confirmed by expression data from both our laboratory and an array-based expression database. Taken together, these results suggest that ZNF76 rs10947540 is a possible susceptibility factor associated with SLE susceptibility. The mechanism underlying the relationship between ZNF76 and SLE pathogenesis still requires further investigation.

Objectives To evaluate a potential role of albumin-to-globulin ratio (AGR) in the development of lupus nephritis (LN) and determine the potential to use AGR as a marker for future LN in systemic lupus erythematosus (SLE) patients. Methods 194 newly diagnosed SLE patients without renal impairment were followed. The clinical data were collected and analyzed at the time of initial diagnosis of SLE and the end of follow-up. We compared baseline characteristics between those who did or did not develop LN on follow-up. Univariate and multivariate Cox hazard analysis were used to identify predictors of lupus nephritis. Results Among the 194 newly diagnosed SLE patients without renal impairment, 26 (13.40%) patients were diagnosed with LN during a median follow-up of 53.87 months. On univariate Cox analysis, patients with the history of alopecia, higher SBP, lower AGR, lower CRP, lower C3, lower C4, higher anti-dsDNA Ab, presence of ANA homogeneous patterns or higher SLEDAI had an increased probability of developing LN. In a multivariate model, the history of alopecia (adjust hazard ratio, aHR = 3.614, 95%CI 1.365-9.571 P = 0.010), lower AGR (aHR = 6.968, 95%CI 1.873-25.919, P = 0.004), lower CRP (aHR = 4.230, 95%CI 1.591-11.247, P = 0.004) and higher level of anti-dsDNA (aHR = 2.675, 95%CI 1.008-7.093, P = 0.048) were independently associated with an increased risk of developing LN after adjusting for covariates. Conclusion Our findings indicated that SLE patients with low AGR, low CRP, high anti-dsDNA and the history of alopecia were more likely to develop LN in the course of SLE. AGR shown the greatest hazard for developing LN among them, it may be a strong predictor.

Objectives: Clinical benefits of immune-checkpoint blockade (ICB) versus standard chemotherapy have been established in unselected non-small cell lung cancer (NSCLC). However, the response to ICB therapy among patients is heterogeneous in clinical practice. Materials and Methods: We retrospectively assessed the predicitive effect of the primary and metastatic lesion spectrum (baseline sum of the longest diameters [SLD], number of metastatic sites and specific organ metastases) on the efficacy of atezolizumab over docetaxel in OAK and POPLAR trial cohorts. A decision model, termed DSO (Diameter-Site-Organ), based on the spectrum was developed and validated for guiding ICB. Results: Higher SLD (>38 mm) and more metastatic sites (≥2) were characterized with pronounced overall survival (OS) benefits from atezolizumab versus docetaxel. Specifically, adrenal gland and brain metastases were identified as favorable predictors of atezolizumab treatment. The DSO model was developed in the discovery cohort to integrate the directive effect of the primary and metastatic lesion spectrum. Remarkably, a general pattern of enhanced efficacy of atezolizumab versus docetaxel was observed along with the increase of the DSO score. For patients with DSO score > 0, atezolizumab yielded a significantly prolonged OS than docetaxel, whereas OS was generally similar between two treatments in patients with DSO score ≤ 0. Equivalent findings were also seen in the internal and external validation cohorts. Conclusions: The response to anti-PD-L1 therapy among patients varied with the primary and metastatic lesion spectrum. The DSO-based system might provide promising medication guidance for ICB treatment in NSCLC patients.

UKRI/STFC’s Scientific Computing Department (SCD) has a long and rich history of delivering face to face public engagement and outreach, both on site and in public places, as part of the wider STFC programme. Due to the global COVID-19 pandemic, SCD was forced to abandon an extensive planned programme of public engagement, alongside altering the day-to-day working methods of the majority of its staff. SCD had to respond rapidly to create a new, remote only, programme for the summer and for the foreseeable future. This was initially an exercise in improvisation, identifying existing activities that could be delivered remotely with minimal changes. As the pandemic went on, SCD also created new resources specifically for a remote audience and adapted existing activities where appropriate, using our evaluation framework to ensure these activities continued to meet the aims of the in-person programme. This paper presents the process through which this was achieved, some of the benefits and challenges of remote engagement and the plans for 2021 and beyond.

Lymphatic malformation is a benign lesion, seldom affecting the gingiva. Gingival lesions are characterized by pebbly hyperplasia, occasional pain, and bleeding. The treatment for large and exceptional areas of involvement may face difficulties. Herein we report a rare case of gingival lymphatic malformation in a 10-year-old girl.

Wearable electronics play a crucial role in advancing the rapid development of artificial intelligence, and as an attractive future vision, all-in-one wearable microsystems integrating powering, sensing, actuating and other functional components on a single chip have become an appealing tendency. Herein, we propose a wearable thermoelectric generator (ThEG) with a novel double-chain configuration to simultaneously realize sustainable energy harvesting and multi-functional sensing. In contrast to traditional single-chain ThEGs with the sole function of thermal energy harvesting, each individual chain of the developed double-chain thermoelectric generator (DC-ThEG) can be utilized to scavenge heat energy, and moreover, the combination of the two chains can be employed as functional sensing electrodes at the same time. The mature mass-fabrication technology of screen printing was successfully introduced to print n-type and p-type thermoelectric inks atop a polymeric substrate to form thermocouples to construct two independent chains, which makes this DC-ThEG flexible, high-performance and cost-efficient. The emerging material of silk fibroin was employed to cover the gap of the fabricated two chains to serve as a functional layer for sensing the existence of liquid water molecules in the air and the temperature. The powering and sensing functions of the developed DC-ThEG and their interactions were systematically studied via experimental measurements, which proved the DC-ThEG to be a robust multi-functional power source with a 151 mV open-circuit voltage. In addition, it was successfully demonstrated that this DC-ThEG can convert heat energy to achieve a 3.3 V output, matching common power demands of wearable electronics, and harvest biothermal energy to drive commercial electronics (i.e., a calculator). The integration approach of powering and multi-functional sensing based on this new double-chain configuration might open a new chapter in advanced thermoelectric generators, especially in the applications of all-in-one self-powered microsystems. A wearable thermoelectric device enables energy generation and sensing for health monitoring. Flexible electronic devices are promising candidates for personal health monitoring, and the ideal device would combine multiple functions in a single device. Two of the most important of these functions are energy generation and sensing. In this paper a team from University of Electronic Science and Technology of China led by Xiao-Sheng Zhang reports a thermoelectric-based device that combines these functions. Based on screen printing technology, they prepare n-type and p-type inorganic films onto a flexible polymer substrate, with their device being able to generate a voltage of up to 151 mV driven by a thermoelectric effect. The water sensitivity and temperature sensitivity of silk fibroin contained in the device enables moisture and temperature to be sensed.

Several studies have investigated a potential association between the endothelial lipase gene (LIPG) 584C/T polymorphism and susceptibility to coronary artery disease (CAD), but a uniform conclusion is yet to be reached. To better evaluate the true relationship between the LIPG 584C/T polymorphism and the risk of CAD, a meta-analysis of 14 case–control studies with 9731 subjects was performed. Relevant articles published through August 2020 were searched in the CNKI, PubMed, Embase and Web of Science databases. Thirteen articles, including 14 eligible case–control studies with 4025 cases and 5706 controls, were enrolled in the present meta-analysis. The Newcastle–Ottawa Scale (NOS) scores of the case–control studies ranged from 6 to 8. The pooled results indicated that there is a significant association between the LIPG 584C/T polymorphism and CAD in the homozygote comparison model and the allelic comparison model. Subgroup analyses revealed that the LIPG 584C/T mutation significantly decreased the risk of CAD in the subgroups of African, CAD, hospital-based (HB), and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) populations in some genetic models. No publication bias was found in our meta-analysis, which certifies the robustness of the current meta-analysis. Trial sequential analysis (TSA) also confirmed the stability of our results. The results of our meta-analysis indicate that the LIPG 584C/T polymorphism plays a protective role in the incidence of CAD. More high-quality case–control studies on various ethnicities are needed to confirm our results.

Percutaneous ethanol injection is a well-known ablation therapy for hepatocellular carcinoma and is well-tolerated, inexpensive, and effective with few adverse events. In this study, another type of ethanol injection was introduced in the present study. Sixty two patients with hepatocellular carcinoma received 133 percutaneous peritumor ethanol injection treatments and the 15-year follow-up outcomes were analyzed through a collected database. The technical efficiency was 89.5% (119/133 treatments) after the first percutaneous peritumor ethanol injection procedure. However, after the second repeated percutaneous peritumor ethanol injection procedure, technical efficiency increased to 98.5% (131/133 treatments). The 1 year, 3 years, 5 years, 10 years, and 15 years rates of tumor recurrence were 12.9%, 50.0%, 59.7%, 74.2%, and 74.2%, respectively. Multivariate analysis demonstrated that diabetes, Child–Pugh class B, and tumor size greater than 2 cm were significantly related to tumor recurrence. The 1 year, 3 years, 5 years, 10 years, and 15 years rates of overall survival were 98.4%, 83.6%, 61.3%, 19.4%, and 0%, respectively. Multivariate analysis demonstrated that Child–Pugh class B, tumor size greater than 2 cm, and multiple tumors were significantly related to overall survival. Compared with other ablation methods (including peritumor ethanol injection), percutaneous peritumor ethanol injection can avoid tumor ruptures, reduce tumor proliferation and metastasis, and is suitable for the treatment of small tumors. In addition, when combined with other treatment methods, percutaneous peritumor ethanol injection can form a tumor metastatic isolation zone in advance and improve the comprehensive treatment effect.

Background: The causal relationship between serum lipid levels and the risk of Parkinson's disease (PD) remains largely uncertain. We summarized the existing controversial evidence on this topic. Methods: We searched the electronic databases for observational studies from January 1988 to March 2020. We applied random-effects models to calculate pooled relative risk (RR) with their 95% confidence intervals (CI). Random-effects dose-response meta-analyses were further conducted to explore the dose-risk relationship. Results: Twelve cohort studies and three case-control studies were included in this meta-analysis. Higher levels of serum low-density lipoprotein cholesterol (LDL-C) were inversely associated with the subsequent risk of PD (RR 0.73, 95% CI 0.57–0.93), whereas, there were no associations between serum levels of total cholesterol (TC) (RR 0.91, 95% CI 0.73–1.13), high-density lipoprotein cholesterol (HDL-C) (RR 0.97, 95% CI 0.73–1.27), or triglycerides (TG) (RR 0.85, 95% CI 0.55–1.29) and the risk of PD. Further dose-response meta-analysis revealed that every 38.6 mg/dL (1mmol/L) increase in serum LDL-C correlates with a 7% decreased risk of PD. Conclusions: Our paper supports the protective effect of higher serum LDL-C on the subsequent risk of PD. More prospective cohort studies are warranted to confirm the conclusion, and further fundamental researches are needed to elucidate the underlying biological mechanisms.

BackgroundGenetic variations of some driver genes in non-small cell lung cancer (NSCLC) had shown potential impact on immune microenvironment and associated with response or resistance to programmed cell death protein 1 (PD-1) blockade immunotherapy. We therefore undertook an exploratory analysis to develop a genomic mutation signature (GMS) and predict the response to anti-PD-(L)1 therapy.MethodsIn this multicohort analysis, 316 patients with non-squamous NSCLC treated with anti-PD-(L)1 from three independent cohorts were included in our study. Tumor samples from the patients were molecularly profiled by MSK-IMPACT or whole exome sequencing. We developed a risk model named GMS based on the MSK training cohort (n=123). The predictive model was first validated in the separate internal MSK cohort (n=82) and then validated in an external cohort containing 111 patients from previously published clinical trials.ResultsA GMS risk model consisting of eight genes (TP53, KRAS, STK11, EGFR, PTPRD, KMT2C, SMAD4, and HGF) was generated to classify patients into high and low GMS groups in the training cohort. Patients with high GMS in the training cohort had longer progression-free survival (hazard ratio (HR) 0.41, 0.28–0.61, p<0.0001) and overall survival (HR 0.53, 0.32–0.89, p=0.0275) compared with low GMS. We noted equivalent findings in the internal validation cohort and in the external validation cohort. The GMS was demonstrated as an independent predictive factor for anti-PD-(L)1 therapy comparing with tumor mutational burden. Meanwhile, GMS showed undifferentiated predictive value in patients with different clinicopathological features. Notably, both GMS and PD-L1 were independent predictors and demonstrated poorly correlated; inclusion of PD-L1 with GMS further improved the predictive capacity for PD-1 blockade immunotherapy.ConclusionsOur study highlights the potential predictive value of GMS for immunotherapeutic benefit in non-squamous NSCLC. Besides, the combination of GMS and PD-L1 may serve as an optimal partner in guiding treatment decisions for anti-PD-(L)1 based therapy.

Background Colon cancer is one of the most common and has the highest mortality rate in the world. MicroRNAs (miRNAs) as potential biomarkers play crucial roles in diagnosis, prognosis, and drug-response prediction of colon cancer. Methods In this study, we collected miRNA expression data from the Broad GDAC Firehose and screened specific miRNA-gene pairs after treatment with 5-fluorouracil treatment and used COAD analysis to study the association of miRNAs and inhibitor of the inhibitory genes. Potential drug-related miRNAs were further extracted via hypergeometric testing. Results The results showed that 13,651 miRNA-gene pairs were retrieved, including 242 miRNAs and 5,179 genes. The association between miRNAs and the inhibitor of inhibitory genes DPYD, TYMS, UNG was indicated. We further extracted 4 potential drug-related miRNAs, including hsa-mir-551a, hsa-mir-144, hsa-mir-519b, hsa-mir-506. The miRNA-gene pairs associated with 5-fluorouracil exhibit better prognosis in patients with CRC. Conclusions We expected that up-regulation of hsa-mir-551a, hsa-mir-144, and hsa-mir-506 and down-regulation of hsa-mir-519b would exhibit better prognosis. The findings would underpin the fundamental hypothesis of mi-RNAs being prognostic signal biomarkers in therapy of 5-fluorouracil in CRC.

Ectodermal dysplasia-skin fragility (EDSF) syndrome is a rare autosomal recessive disease characterized by skin fragility, chronic cheilitis, palmoplantar keratoderma, abnormal hair growth and nail dystrophy. EDSF syndrome is caused by mutations in the PKP1 gene encoding plakophilin-1, which result in desmosomal abnormality and poor intercellular cohesion between epidermal cells. Herein, we report a novel homozygous deletion of the PKP1 gene in a Chinese boy with EDSF syndrome. Our study expands the database on PKP1 mutations and emphasizes the key role played by PKP1 in the structure and function of the epidermal desmosomes. In addition, we describe the ultrastructural changes of the curly hair in patients with EDSF syndrome for the first time.

Background: Clinical benefits of immune-checkpoint blockade (ICB) versus standard chemotherapy have been established in unselected non-small cell lung cancer (NSCLC). However, the response to ICB therapy among patients is still heterogeneous in clinical practice. Methods: We retrospectively assessed the impact of baseline sum of the longest diameters (SLD), number of metastatic sites and specific organ metastases on the efficacy of atezolizumab versus docetaxel in the pooled population from OAK and POPLAR studies. An assistant decision model based on the machine-learning method, incorporating these indicators, termed DSO (Diameter-Site-Organ), was developed and validated in OAK and POPLAR cohorts. Findings: Higher SLD (> 38mm) and more metastatic sites (≥ 2) were characterized with pronounced OS benefits from atezolizumab versus docetaxel. Specifically, brain and adrenal gland metastases were identified as favorable predictors of atezolizumab treatment. The DSO model for guiding second-line treatment was developed based on SLD and metastatic sites and organs in the discovery cohort. Remarkably, a general pattern of enhanced efficacy of atezolizumab versus docetaxel was observed along with the increase of the DSO score. For patients with DSO score > 0, atezolizumab yielded a prolonged OS than docetaxel (hazard ratio [HR] 0.67, 95% CI 0.54-0.84; P = 0.0003), whereas OS was generally similar between two treatments in patients with DSO score ≤ 0 (HR 1.46, 95% CI 0.89-2.39; P = 0.1346). Equivalent findings were seen in the internal and external validation cohorts. Interpretation: Our study for the first time revealed that patients with higher tumor burden were more suitable for ICB compared with standard chemotherapy. More importantly, the integrative DSO decision model might provide promising medication guidance for second-line ICB treatment in unselected NSCLC patients. Funding: This study was supported by the National Natural Science Foundation for YoungScientists of China (Grant No. 81802863 and 81902353), the Natural Science Foundation of Guangdong Province (Grant No. 2018030310285), and the Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University (Grant No. 2017J003). Conflict of Interest: The authors have no actual or potential conflicts of interest to declare. Ethical Approval: The study was approved by theInstitutional Ethical Review Boards of Nanfang Hospital. All patients enrolled in OAK and POPLAR provided signed informed consent in accordance with the protocols of the corresponding studies.

Background. Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by apoptotic clearance deficiency provoking autoimmune responses and leading to multiple organ damage. PPAR-δ, encoded by the PPARD gene, was induced in macrophages promoting the timely disposal of apoptotic cells. Biological studies had provided solid foundation of PPARD involvement in SLE; it is worthwhile to further explore the genetic contribution of PPARD to SLE. Methods. We performed a discovery-replication genetic association study. The discovery study was based on previous reported GWAS data. And the replication study was conducted in 1003 SLE patients and 815 healthy controls from Henan, Middle East of China. Further, we analyzed the eQTL effect to identify possible functional significance. Results. In the genetic association analysis, we observed significant association between the risk C allele of rs4713853 (p=0.03, OR 1.167, 95% CI 1.015-1.341) and increased SLE susceptibility. Moreover, individuals with the risk C allele were associated with lower expression of PPARD and DEF6. Our clinical analysis showed that SLE patients with the risk C allele of rs4713853 were more likely to present a higher proportion of anti-Sm antibody presence (CC+CT vs. TT, 20.0% vs. 14.2%, p=0.039) and higher level of Scr (median inter quarter range CC+CT vs. TT, 56 48-71 vs. 54 46-64 μmol/L, p=0.002). Conclusions. In conclusion, our study identified a novel association between PPARD rs4713853 and SLE susceptibility in Chinese populations. By integrating multiple layers of analysis, we suggested that PPARD might be a main candidate in the pathogenesis of SLE.

Background Increasing evidence recognizes that DNA methylation abnormalities play critical roles in cancer development. Our previous genome-wide methylation profile showed that tumor necrosis factor-alpha-induced protein 8 like 3 (TIPE3) was hypermethylated in nasopharyngeal carcinoma (NPC). However, the relationship between TIPE3 methylation and its mRNA expression, as well as its biological roles in NPC are unknown. Methods Bisulfite pyrosequencing and quantitative RT-PCR were performed to quantify the TIPE3 methylation and expression levels. Kaplan-Meier curves and Cox regression analysis were used to estimate the correlation between TIPE3 methylation levels and survival in two patient cohorts collected from two hospitals (n = 441). The MTT, colony formation, Transwell migration and invasion assays, and xenograft tumor growth and lung metastatic colonization models were used to identify the functions of TIPE3 on NPC cells. Results We found that TIPE3 CpG island (CGI) was hypermethylated and its mRNA levels were downregulated in many cancers, including NPC. TIPE3 downregulation was associated with its CGI hypermethylation. Furthermore, NPC patients with high TIPE3 CGI methylation levels had poorer clinical outcomes than those with low methylation levels. The TIPE3 CGI methylation level was an independent prognostic factor. Moreover, restoring TIPE3 expression significantly inhibited NPC cell proliferation, migration and invasion in vitro, and suppressed tumor growth and lung metastatic colonization in vivo, while silencing TIPE3 acted in an opposite way. Conclusions TIPE3 downregulation correlates with its CGI hypermethylation in several solid cancers. TIPE3 acts as a tumor suppressor in NPC, providing a further insight into NPC progression and representing a potential prognostic biomarker for NPC. Electronic supplementary material The online version of this article (10.1186/s13046-018-0881-5) contains supplementary material, which is available to authorized users.

Purpose: Epigenetic alterations play important roles in metastasis and drug resistance through gene regulation. However, the functional features and molecular mechanisms of epigenetic changes remain largely unclear in nasopharyngeal carcinoma (NPC) metastasis. Experimental Design: Gene regulatory network analysis was used to identify metastatic-specific dysregulated genes between normal and NPC tissues and the expression was validated in published Gene-Expression Omnibus data set. The regulatory and functional role of RAB37 downregulation was examined in NPC and was validated in vitro and in vivo, and downstream target of RAB37 was explored. The clinical value of RAB37 methylation was evaluated in NPC metastasis and chemosensitivity. Results: We identified RAB37 as a specific hypermethylated gene that is most commonly downregulated in NPC. Moreover, RAB37 downregulation was attributed to hypermethylation of its promoter and was significantly associated with metastasis- and docetaxel chemoresistance-related features in NPC. Ectopic RAB37 overexpression suppressed NPC cell metastasis and enhanced chemosensitivity to docetaxel. Mechanistically, RAB37 colocalized with TIMP2, regulated TIMP2 secretion, inhibited downstream MMP2 activity, and consequently altered NPC cell metastasis. Furthermore, RAB37 hypermethylation was correlated with poor clinical outcomes in patients with NPC. We developed a prognostic model based on RAB37 methylation and N stage that effectively predicted an increased risk of distant metastasis and a favorable response to docetaxel-containing induction chemotherapy (IC) in NPC patients. Conclusions: This study shows that RAB37 hypermethylation is involved in NPC metastasis and chemoresistance, and that our prognostic model can identify patients who are at a high risk of distant metastasis and might benefit from for docetaxel IC.

In order to realize the image fusion of multi focus and multi-source acquisition, in this paper a method based on deep learning model and DT-CWT image fusion is proposed. Firstly, the base parts and detail features of the image were separated, the base parts was denoised and filtered by DT-CWT, and the fusion base parts were obtained; depth learning model VGG-S was selected to extract the detail features of the image, and then the fusion details were obtained by multi-layer fusion strategy. Finally, the maximum gradient value is used to select the detail features to obtain the fusion details. The fusion base parts and details features were overlapped and reconstructed to obtain the fusion image. The algorithm not only retains the significant features of the image, but also makes the fused image obtain more detailed feature information. In the process, the noise was reduced. The subjective and objective evaluation results are improved obviously.

There is a growing demand for wearable electronic devices in recent years. In particular, stretchable strain sensors with large strain range, high sensitivity, good linearity and remarkable stability have attracted much attention in wearable electronics field for applications in the real-time human motion detection. However, the simultaneous realization of high stretchability and good sensitivity is still a critical challenge, especially in the consideration of the conformability on the curved surfaces. In this work, a fully-stretchable and highly- sensitive strain sensor with outstanding profile conformability was developed by using a novel liquid-state conductive composite composed of carbon nanotubes and liquid silicone rubber. This liquid-state conductive composite exhibits a remarkable stretchability and stability compared with traditional stretchable electrodes, which endows the strain sensor a 400% length deformation with a gauge factor of 43.84. Moreover, the proposed strain sensor was systematically studied and proven to possess the unique features of high linearity, low hysteresis and good stability. The strain sensor can endure various mechanical deformations without any damage, including 4-folded, and 360° twisted. It was also demonstrated that the developed sensor can monitor the gesture and motion of joint activities, which shows an attractive future vision for applications in health detection.

Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma.In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival.We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; p0·0001), disease-free survival (HR 3·51, 2·43-5·07; p0·0001), and overall survival (HR 3·22, 2·18-4·76; p0·0001) than patients with low-risk scores. The prognostic accuracy of DMGN was validated in the internal and external cohorts. Furthermore, among patients with low-risk scores in the combined training and internal cohorts, concurrent chemotherapy improved distant metastasis-free survival compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19-0·83; p=0·011), whereas patients with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71-1·50; p=0·876). This was also validated in the two external cohorts combined. We developed a nomogram based on the DMGN and other variables that predicted an individual's risk of distant metastasis, which was strengthened by adding Epstein-Barr virus DNA status.The DMGN is a reliable prognostic tool for distant metastasis in patients with locoregionally advanced nasopharyngeal carcinoma and might be able to predict which patients benefit from concurrent chemotherapy. It has the potential to guide treatment decisions for patients at different risk of distant metastasis.The National Natural Science Foundation of China, the National ScienceTechnology Pillar Program during the Twelfth Five-year Plan Period, the Natural Science Foundation of Guang Dong Province, the National Key Research and Development Program of China, the Innovation Team Development Plan of the Ministry of Education, the HealthMedical Collaborative Innovation Project of Guangzhou City, China, and the Program of Introducing Talents of Discipline to Universities.

The American Joint Committee on Cancer (AJCC) staging system is inadequate for an accurate prognosis in nasopharyngeal carcinoma (NPC). Thus, new biomarkers are under intense investigation. Here, we investigated whether the density of TILs could predict prognosis in NPC. First, we used 1490 cases of nasopharyngeal carcinoma samples from two independent cohorts to evaluate the density and distribution of tumor-infiltrating lymphocytes (TILs). Second, in one cohort, we assessed associations between TILs and clinical outcomes in 593 randomly selected samples (defined as the training set) and validated findings in the remaining 593 samples (defined as the validation set). Furthermore, we confirmed the prognostic value of TILs in a second independent cohort of 304 cases (defined as the independent set). Based on multivariable Cox regression analysis, we also established an effective prognostic nomogram including TILs to improve accuracy in predicting disease-free survival (DFS) for patients with nondisseminated NPC. We found that high TILs in the training set were significantly associated with favorable DFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.58, p < 0.001], overall survival (OS, HR 0.42, 95% CI 0.27-0.64, p < 0.001), distant metastasis-free survival (DMFS, HR 0.37, 95% CI 0.23-0.58, p < 0.001) and local-regional recurrent free survival (LRRFS, HR 0.43, 95% CI 0.25-0.73, p = 0.002). Multivariate analysis showed that TILs are an independent prognostic indicator for DFS in all cohorts. In summary, this study indicated that TILs may reflect the immunological heterogeneity of NPC and could represent a new prognostic biomarker.

The goal of this study is to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese non-small cell lung cancer (NSCLC) patients to inform the clinical development of anti-PD1/PD-L1 agents in this population. We used phosphatase and tensin homolog (PTEN) expression through IHC as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were then analyzed with a clinically validated PD-L1 IHC assay. The results were correlated with baseline characteristics and clinical outcomes. PTEN IHC showed that 108 TMA samples and 105 whole-section samples qualified for PD-L1 IHC. With a clinically relevant cutoff, 41.7% of the TMA samples were PD-L1 positive. PD-L1 level was much lower in EGFR-mutant patients and seemed to be a favorable prognostic factor for both overall survival (OS) and recurrence-free survival (RFS). These findings were confirmed in the whole-section samples except that their survival data were not mature enough for correlation analysis. In summary, PD-L1 expression was detected in approximately 40% of PTEN-qualified Chinese NSCLC samples, negatively correlated with EGFR mutation and seemed to be a favorable prognostic factor for both OS and RFS. Notably, the different results from PTEN-qualified and PTEN-disqualified samples underscore the importance of tissue quality control prior to biomarker testing.

Stretchable triboelectric nanogenerators (TENGs) attract much attentions in the field of wearable electronics owing to their unique capabilities of ambient energy harvesting, especially from human activities, serving as sustainable power source as well as functional sensing device. The essential challenge of super-stretchable triboelectric nanogenerator (SS-TENG) is to overcome the non-stretchable drawback of conventional electrodes and endow them with remarkable extension capability. In this work, we developed a carbon nanotubes (CNT)-silicone rubber liquid composite with outstanding conductivity and fluidity, which provides an essential opportunity to realize a SS-TENG with the remarkable capability of 900% stretchable deformation. This newly developed SS-TENG successfully achieved the integration of bio-mechanical energy harvesting and multi-functional sensing. The electric output performance was comprehensively investigated and a maximum power density of 21.7 W/m2 was obtained, which is large enough to power common low-power-consumption electronic devices. As for passive sensing, the proposed SS-TENG can be utilized as a strain gauge with good sensitivity (gauge factor (GF) of 11.4) and low hysteresis (degree of hysteresis (DH) of 0.71%). Moreover, as for active sensing, the detection of dynamic motions of human body joints was realized due to the correlation between gesture and corresponding electrical signal. Eventually, a self-powered wearable keyboard based on SS-TENG arrays with outstanding conformability on curved surfaces was demonstrated, which reveals a promising potential of the proposed liquid conductive composite and the developed SS-TENG for self-powered wearable electronic applications, especially in the healthcare field.

As an emerging ambient energy harvesting technology, triboelectric nanogenerators (TENGs) have been proven as robust power sources, and furthermore self-powered electronics which are promising to construct human-machine interfaces due to the unique feature of the integration of powering itself and functionalities. Several technologies have been proposed to improve the properties of TENGs, but most of them focus on the interface of triboelectric pair and rarely on another key component, the electrodes. Here, a new configuration of TENG array based on the electrode-miniaturized strategy is developed. The effects of the electrode miniaturization on the electrical output, optical transmittance and signal interference are comprehensively investigated through experimental measurements. It reveals that two-third reduction in the electrode area only exhibits a slight effect on the electrical output of TENG, in other words the proposed electrode-miniaturized TENGs (EM-TENGs) keep highly consistent while the electrode area tuning in the range of 33–100%. Moreover, this electrode-miniaturized strategy endows TENGs two more significant benefits, including higher light transmittance and lower signal interference, which makes it show much greater potential in the field of self-powered smart microsystems, especially in need of remarkable optical properties. Therefore, a human-machine interaction microsystem for trajectory tracking is successfully demonstrated, which is self-powered, transparent and flexible.