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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.

Multiple studies on the pathomechanisms of depressive disorder and antidepressants have been reported. However, literature involving scientometric analysis of depressive disorder is sparse. Here, we use scientometric analysis and a historical review to highlight recent research on depression. We use the former to examine research on depressive disorders from 1998 to 2018. The latter is used to identify the most frequent keywords in keyword analysis, as well as explore hotspots and depression trends. Scientometric analysis uncovered field distribution, knowledge structure, research topic evolution, and topics emergence as main explorations in depressive disorder. Induction factor, comorbidity, pathogenesis, therapy and animal models of depression help illustrate occurrence, development and treatment of depressive disorder. Scientometric analysis found 231,270 research papers on depression, a 4-fold increase over the last 20 years. These findings offer a vigorous roadmap for further studies in this field.

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.

Culex tritaeniorhynchus Gile is a major vector of Japanese encephalitis in China. The population genetics study is crucial as it helps understanding the epidemiological aspects of mosquito-brone di...

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:. 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.

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.

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.

Background Dysregulation of T cells mediated immune responses is a hallmark in the development of systemic lupus erythematosus (SLE). Recent genome wide association study (GWAS) revealed the genetic contribution of variants located in the cytotoxic T lymphocyte-associated protein-4 (CTLA4)-inducible T cell co-stimulator (ICOS) intergenic region to SLE susceptibility. Our aim is to find a functional variant in this region. Methods The genetic association results in the CTLA4-ICOS region from previous GWAS were adopted to select the potential variant which was further replicated in two independent cohorts (Henan cohort 2053 SLE patients and 1845 healthy controls, Beijing cohort 2303 SLE patients and 19,262 healthy). In order to explore the functional significance in SLE, bioinformatics with validation experiments (including electrophoretic mobility shift assay and luciferase reporter assay) and mRNA expression analysis were also performed. Results A variant located in the CTLA4-ICOS intergenic region, rs17268364, was associated with susceptibility to SLE patients in Chinese populations (risk allele, pmeta = 7.02×10−11, OR 1.19, 95%CI 1.13–1.26). The bioinformatics suggested that rs17268364 might affect the expression of CTLA4, not ICOS. The rs17268364 risk G allele containing sequence reduced the expression of the reporter gene by binding transcriptional repressor Ewing sarcoma breakpoint region 1 (EWSR1). Following genotype-mRNA expression, the analysis also showed the risk allele of rs17268364 was associated with low CTLA4 expression in lupus nephritis (LN) patients. Healthy individuals carrying rs17268364 risk G allele was significantly correlated with higher levels of IFN-α signature including increased lymphocyte antigen 6E (LY6E) (p=0.031), interferon-stimulated gene 15 (ISG15) (p=0.038), interferon regulatory factor 9 (IRF9) (p=0.028), and interferon regulatory factor 5 (IRF5) (p=0.040) mRNA expression. Conclusions The present study confirmed the functional role of rs17268364 in the CTLA4-ICOS intergenic region that increased SLE susceptibility in the Chinese population.

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.

Mastitis causes great psychological and physical pain among women. Our previous studies found that niacin has anti-inflammatory effect, and the realization of this function depends on GPR109A. However, there are no previous reports about the anti-inflammatory function of GPR109A in mastitis. In our study, we observed the effect of niacin on the WT and GPR109A-/- mice mastitis model. The results showed that administration of niacin to WT mice reduced the damage, proinflammatory mediators and protected the integrity of the blood milk barrier in mammary gland. While in GPR109A-/- mice, there was no effect on the above indexes. In mammary epithelial cells, GPR109A was able to promote autophagy and Nrf2 nuclear import through AMPK. In LPS-induced mammary epithelial cells, niacin inhibited the LPS-induced inflammatory response and downregulation of tight junction proteins, and these effects were eliminated by knocking down GPR109A, blocking autophagy or inhibiting Nrf2 nuclear import. These results indicate that in mastitis, GPR109A promotes autophagy and Nrf2 nuclear import through AMPK, thereby inhibiting inflammatory damage to the mammary gland and repairing the blood milk barrier. Our results suggested that GPR109A may be a potential target for the treatment of mastitis.

Altered DNA methylation is a key feature of cancer, and aberrant methylation is important in nasopharyngeal carcinoma (NPC) development. However, the methylation mechanisms underlying metastasis of NPC remain unclear. Analyzing data from public databases and conducting our own experiments, we report here that promoter hypermethylation of SHISA3 is common and contributes to the downregulation of this gene in many types of tumors, including NPC. SHISA3 suppressed NPC cell invasion and metastasis in vitro and in vivo by impeding the E3 ubiquitin ligase tripartite motif containing 21 (TRIM21)–mediated ubiquitination and degradation small G protein signaling modulator 1 (SGSM1) and by inhibiting the MAPK pathway activation. Silencing SGSM1 abrogated the inhibitory effect of SHISA3 on NPC cell migration and invasion. This newly identified SHISA3–TRIM21–SGSM1 axis could be a novel therapeutic target in NPC. Significance: These findings highlight the mechanism by which a newly identified tumor suppressor SHISA3 suppresses invasion and metastasis of nasopharyngeal carcinoma.

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.

BackgroundAlzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline, psychiatric symptoms and behavioral disorders, resulting in disability and loss of self-sufficiency.ObjectiveTo establish an AD mice model, investigate the behavioral performance, and explore the potential mechanism.MethodsStreptozotocin (STZ, 3 mg/kg) was microinjected bilaterally into the dorsal hippocampus of C57BL /6 mice to establish the AD model. Behavioral changes (anhedonia and despair, balance and motor coordination, locomotion, and learning and memory) were examined and the serum concentrations of insulin and nesfatin-1 were measured by ELISA. The activation of hippocampal microglia was assessed by immunohistochemistry and the protein expression of several molecular associated with the regulation of synaptic plasticity in the hippocampus and the prefrontal cortex (PFC) was detected via western blotting.ResultsThe STZ model mice showed a slower bodyweight gain and higher serum concentration of insulin and nesfatin-1. Although there was no significant difference between groups with regard to the ability of balance and motor coordination, the model mice presented a decline of spontaneous movement and exploratory behavior, together with an impairment of learning and memory ability. Increased activated microglia was aggregated in the hippocampal dentate gyrus of model mice. Moreover, the protein expression of NMDAR2A, NMDAR2B, SynGAP, PSD95, BDNF, and p-β-catenin/β-catenin were remarkably decreased in the hippocampus and the PFC of model mice, and the expression of p-GSK-3β (ser9)/GSK-3β were reduced in the hippocampus.ConclusionA bilateral hippocampal microinjection of STZ could successfully duplicate an AD mice model, as indicated by the impaired learning and memory and the alternated synaptic plasticity, together with the hyperactive inflammatory response in the hippocampus and the imbalanced abundance of serum insulin and nesfatin-1. Apart from these, the mechanism might be associated with the imbalanced expression of the key proteins of Wnt signaling pathway in the hippocampus and the PFC.Graphical abstract

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.

Leukemia arises from blockage of the differentiation/maturation of hematopoietic progenitor cells at different stages with uncontrolled proliferation of leukemic cells. However, the signal pathways that block cell differentiation remain unclear. Herein we found that SUMOylation of the M2 isoform of pyruvate kinase (PKM2), a rate-limiting glycolytic enzyme catalyzing the dephosphorylation of phosphoenolpyruvate to pyruvate, is prevalent in a variety of leukemic cell lines as well as primary samples from patients with leukemia through multiple-reaction monitoring based targeted mass spectrometry analysis. SUMOylation of PKM2 lysine 270 (K270) triggered conformation change from tetrameric to dimeric of PKM2, reduced PK activity, and led to nuclear translocation of PKM2. SUMO1 modification of PKM2 recruits and promotes degradation of RUNX1 via a SUMO-interacting motif, resulting in blockage of myeloid differentiation of NB4 and U937 leukemia cells. Replacement of wild type PKM2 with a SUMOylation-deficient mutant (K270R) abrogated the interaction with RUNX1, and the blockage of myeloid differentiation in vitro and in xenograft model. Our results establish PKM2 as an essential modulator of leukemia cell differentiation and a potential therapeutic target, which may offer synergistic effect with differentiation therapy in the treatment of leukemia.

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.

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.

α-Cyperone, extracted from Cyperus rotundus, has been reported to inhibit microglia-mediated neuroinflammation. Oxidative stress and apoptosis play crucial roles in the course of Parkinson's disease (PD). PD is a common neurodegenerative disease characterized by selective death of dopaminergic neurons. This study was designed to investigate the neuroprotective effects of α-cyperone against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in dopaminergic neuronal SH-SY5Y cells. Neurotoxicity was assessed by MTT assay and the measurement of lactic dehydrogenase (LDH) release. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. The apoptosis of SH-SY5Y cells was evaluated by annexin-V-FITC staining. The translocation of NF-E2-related factor 2 (Nrf2) was determined by western blot and immunofluorescence staining. Western blot analysis was conducted to determine the expression level of cleaved-caspase-3, the pro-apoptotic factor Bax, and the anti-apoptotic factor, Bcl-2. The results showed that α-cyperone substantially decreased H2O2-induced death, release of LDH, and the production of ROS in SH-SY5Y cells. In addition, we found that α-cyperone attenuated H2O2-induced cellular apoptosis. Moreover, α-cyperone remarkably reduced the expression of cleaved-caspase-3 and Bax, and upregulated Bcl-2. Furthermore, α-cyperone enhanced the nuclear translocation of Nrf2. Pretreatment with brusatol (BT, an Nrf2 inhibitor) attenuated α-cyperone-mediated suppression of ROS, cleaved-caspase-3, and Bax, as well as α-cyperone-induced Bcl-2 upregulation in H2O2-treated SH-SY5Y cells. α-cyperone neuroprotection required Nrf2 activation. In conclusion, α-cyperone attenuated H2O2-induced oxidative stress and apoptosis in SH-SY5Y cells via the activation of Nrf2, suggesting the potential of this compound in the prevention and treatment of PD.

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.

Previous study has identified SLC7A14 as a new causative gene of retinitis pigmentosa (RP). However, the role of SLC7A14 has not been fully characterized. The goal of this study was to investigate the biological features of slc7a14 in zebrafish. To determine the expression of slc7a14 in developing zebrafish, we performed in situ hybridization (ISH) and quantitative real-time PCR. Morpholino knockdown and overexpression experiments were performed to study the role of slc7a14 in zebrafish retinas. Immunostaining was carried out to observe structural changes. Visual motor responses (VMR) and optokinetic responses (OKR) were analyzed to assess visual behaviors. Terminal deoxynucleotidyl transferase (dUTP) nick-end labeling (TUNEL) staining was performed to survey apoptotic retinal cells. We found that slc7a14 was highly expressed in neuronal tissues, including the brain, spinal cord and retina, and that the expression levels increased during early embryogenesis. Consistently, ISH showed a similar expression pattern. Knockdown of slc7a14 led to dose-dependent microphthalmia that was reversed by overexpression. The immunostaining results revealed that the rod-specific protein zpr-3 and the retinal pigment epithelium-specific protein zpr-2 (decreased to 44.48%) were significantly suppressed in the slc7a14-silenced morphants. Notably, visual behaviors (the VMR and the OKR) were severely impaired in the slc7a14-deficient morphant, especially the VMR OFF response. In addition, apoptotic cells were observed in the retina at 3 days post fertilization (dpf) and 5 dpf by TUNEL assay. Our results demonstrated that slc7a14 is essential for visually mediated behaviors in zebrafish. Temporary silencing of slc7a14 in larvae led to severe visual impairments, consistent with the manifestations observed in RP patients. Our findings provide further insights into the genetic mechanisms of RP predisposition caused by SLC7A14 mutations.

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.

G Protein Coupled Receptor 109A (GPR109A), which belongs to the G protein coupled receptor family, can be activated by niacin, butyrate, and β-hydroxybutyric acid. Here, we assessed the anti-inflammatory activity of sodium butyrate (SB) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mice, an experimental model that resembles Crohn's disease, and explored the potential mechanism of SB in inflammatory bowel disease (IBD). In vivo, experimental GPR109a−/− and wild-type (WT) mice were administered SB (5 g/L) in their drinking water for 6 weeks. The mice were then administered TNBS via rectal perfusion to imitate colitis. In vitro, RAW246.7 macrophages, Caco-2 cells, and primary peritoneal macrophages were used to investigate the protective roles of SB on lipopolysaccharide (LPS)-induced inflammatory response and epithelium barrier dysfunction. In vivo, SB significantly ameliorated the inflammatory response and intestinal epithelium barrier dysfunction in TNBS-induced WT mice, but failed to provide a protective effect in TNBS-induced GPR109a−/− mice. In vitro, pre-treatment with SB dramatically inhibited the expression of TNF-α and IL-6 in LPS-induced RAW246.7 macrophages. SB inhibited the LPS-induced phosphorylation of the NF-κB p65 and AKT signaling pathways, but failed to inhibit the phosphorylation of the MAPK signaling pathway. Our data indicated that SB ameliorated the TNBS-induced inflammatory response and intestinal epithelium barrier dysfunction through activating GPR109A and inhibiting the AKT and NF-κB p65 signaling pathways. These findings therefore extend the understanding of GPR109A receptor function and provide a new theoretical basis for treatment of IBD., Highlights • Sodium butyrate maintains the gut epithelium barrier and protects against inflammation in TNBS-induced colitis-model mice • Targeting GPR109A anti-inflammatory and pro-intestinal epithelium barrier functions is a new strategy for IBD treatment Butyrate, produced by microbial fermentation in the bowel, has a protective effect toward maintaining the integrity of the gut epithelium barrier, which can decrease inflammatory responses in inflammatory bowel disease (IBD) such as Crohn's disease, although the underlying mechanism remains unknown. Here, we used cell and animal models of colitis to demonstrate that butyrate-mediated activation of the GPR109A receptor, which is known to suppress the inflammatory effects in various diseases, underlies its protective effects on colon health. Our results demonstrate that activating GPR109A thus may represent a novel approach to treat IBD, for which effective treatments are urgently required.

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.

Toxoplasma gondii, a protozoan intracellular parasite, is present in a wide range of hosts, including virtually all species of warm-blooded vertebrates. Toxoplasmosis spreads to humans through a variety of pathways, including contaminated food or water, and close contact with various types of domestic animals. It poses a severe threat to human health, and contributes to important economic losses, not only in cost-of-illness but also in surveillance programs. It is thus necessary to develop a rapid point-of-care field diagnostic technology to control or prevent pathogen transmission to economically important livestock animals, domestic animals, and human beings. In this study, we develop a real-time isothermal amplification method capable of detecting the T. gondii genome in swine and feline blood samples. This method can detect toxoplasma genome with a lowest detection limit of 102 copies of per reaction under optimal reaction conditions of 36 °C for 25 min. The assay displayed advantages in sensitivity and specificity in comparison to traditional real-time PCR, and can be performed in a portable instrument.

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.

Objectives To investigate the feasibility of contralateral lower neck sparing intensity modulation radiated therapy (IMRT) for nasopharyngeal carcinoma patients (NPC) with unilateral cervical lymph node metastasis. Materials and methods Retrospective review of 546 patients with unilateral cervical lymph node metastasis treated between November 2009 and February 2012 at one institution. All patients were staged using magnetic resonance imaging and received radical IMRT. Patients were classified into two groups: the inferior border of the negative neck irradiation field only covered Levels III to Va in Group 1; the inferior border covered entire neck down to Levels IV to Vb in Group 2. Results Median follow-up was 49.9 months (range, 1.3–69.2 months). Four-year overall survival (OS:89.3% vs. 88.9%, P = 0.91), disease-free survival (DFS:81.7% vs. 81.0%, P = 0.91), distant metastasis-free survival (DMFS:88.2% vs. 87.9%, P = 0.95), local relapse-free survival (LRFS:96.7% vs. 94.7%, P = 0.70) and nodal relapse-free survival (NRFS: 96.1% vs. 95.9%, P = 0.94) were not significantly different between Group 1 and Group 2. Twenty-two patients developed cervical lymph node relapse; of whom 20/22 (91.0%) developed unilateral relapse within pretreatment positive neck. Only one patient developed out-of-field relapse, though this patient also relapsed within the neck irradiation field (Level II). No clinicopathological feature tested had significant prognostic value for NRFS in multivariate analysis. Conclusions In the IMRT and MRI era, contralateral lower neck sparing IMRT seems to be feasible for NPC patients with unilateral cervical lymph node metastasis.

Nasopharyngeal carcinoma (NPC) is characterized by a high rate of local invasion and early distant metastasis. Increasing evidence indicates that epigenetic abnormalities play important roles in NPC development. However, the epigenetic mechanisms underlying NPC metastasis remain unclear. Here we investigate aberrantly methylated transcription factors in NPC tissues, and we identify the HOP homeobox HOPX as the most significantly hypermethylated gene. Consistently, we find that HOXP expression is downregulated in NPC tissues and NPC cell lines. Restoring HOPX expression suppresses metastasis and enhances chemosensitivity of NPC cells. These effects are mediated by HOPX-mediated epigenetic silencing of SNAIL transcription through the enhancement of histone H3K9 deacetylation in the SNAIL promoter. Moreover, we find that patients with high methylation levels of HOPX exhibit poor clinical outcomes in both the training and validation cohorts. In summary, HOPX acts as a tumour suppressor via the epigenetic regulation of SNAIL transcription, which provides a novel prognostic biomarker for NPC metastasis and therapeutic target for NPC treatment., HOPX is a transcription factor epigenetically silenced in several cancers. Here the authors, by analysing methylation profiles, identify HOPX as a suppressor of metastasis in nasopharyngeal carcinoma: mechanistically HOPX inhibits SNAIL transcription through deacetylation-mediated silencing.

Objective To compare hospital costs and clinical outcomes between transradial intervention (TRI) and transfemoral intervention (TFI) in elderly patients aged over 65 years. Methods We identified 1229 patients aged over 65 years who underwent percutaneous coronary intervention (PCI) in Fuwai Hospital, Beijing, China, between January 1 and December 31, 2010. Total hospital costs and in-hospital outcomes were compared between TRI and TFI. An inverse probability weighting (IPW) model was introduced to control potential biases. Results Patients who underwent TRI were younger, less often female, more likely to receive PCI for single-vessel lesions, and less likely to undergo the procedure for ostial lesions. TRI was associated with a cost saving of CNY7495 (95%CI: CNY4419-10 420). Such differences were mainly driven by lower PCI-related costs. TRI patients had shorter length of stay (1.9 days, 95%CI: 1.1-2.7 days), shorter post-procedural stay (0.7 days, 95%CI: 0.3-1.1 days), and fewer major adverse cardiac events (adjusted odds ratio = 0.47, 95%CI: 0.31-0.73). There was no statistical significance in the incidence of post-PCI bleeding between TRI and TFI (P>0.05). Such differences remained consistent in clinically relevant subgroups of acute myocardial infarction, acute coronary syndrome, and stable angina. Conclusion The use of TRI in patients aged over 65 years was associated with significantly reduced hospital costs and more favorable clinical outcomes.