Inflammation-Responsive Mesoporous Silica Nanoparticles with Synergistic Anti-inflammatory and Joint Protection Effects for Rheumatoid Arthritis Treatment.

PURPOSE: Joint destruction is a major burden and an unsolved problem in rheumatoid arthritis (RA) patients. We designed an intra-articular mesoporous silica nanosystem (MSN-TP@PDA-GlcN) with anti-inflammatory and joint protection effects. The nanosystem was synthesized by encapsulating triptolide (TP) in mesoporous silica nanoparticles and coating it with pH-sensitive polydopamine (PDA) and glucosamine (GlcN) grafting on the PDA. The nano-drug delivery system with anti-inflammatory and joint protection effects should have good potency against RA. METHODS: A template method was used to synthesize mesoporous silica (MSN). MSN-TP@PDA-GlcN was synthesized via MSN loading with TP, coating with PDA and grafting of GlcN on PDA. The drug release behavior was tested. A cellular inflammatory model and a rat RA model were used to evaluate the effects on RA. In vivo imaging and microdialysis (MD) system were used to analyze the sustained release and pharmacokinetics in RA rats. RESULTS: TMSN-TP@PDA-GlcN was stable, had good biocompatibility, and exhibited sustained release of drugs in acidic environments. It had excellent anti-inflammatory effects in vitro and in vivo. It also effectively repaired joint destruction in vivo without causing any tissue toxicity. In vivo imaging and pharmacokinetics experiments showed that the nanosystem prolonged the residence time, lowered the Cmax value and enhanced the relative bioavailability of TP. CONCLUSIONS: These results demonstrated that MSN-TP@PDA-GlcN sustained the release of drugs in inflammatory joints and produced effective anti-inflammatory and joint protection effects on RA. This study provides a new strategy for the treatment of RA.

The Critical Role of Equilibrative Nucleoside Transporter-2 in Modulating Cerebral Damage and Vascular Dysfunction in Mice with Brain Ischemia-Reperfusion.

BACKGROUND: Cerebral vascular protection is critical for stroke treatment. Adenosine modulates vascular flow and exhibits neuroprotective effects, in which brain extracellular concentration of adenosine is dramatically increased during ischemic events and ischemia-reperfusion. Since the equilibrative nucleoside transporter-2 (Ent2) is important in regulating brain adenosine homeostasis, the present study aimed to investigate the role of Ent2 in mice with cerebral ischemia-reperfusion. METHODS: Cerebral ischemia-reperfusion injury was examined in mice with transient middle cerebral artery occlusion (tMCAO) for 90 minutes, followed by 24-hour reperfusion. Infarct volume, brain edema, neuroinflammation, microvascular structure, regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (CMRO2), and the production of reactive oxygen species (ROS) were examined following the reperfusion. RESULTS: Ent2 deletion reduced the infarct volume, brain edema, and neuroinflammation in mice with cerebral ischemia-reperfusion. tMCAO-induced disruption of brain microvessels was ameliorated in Ent2-/- mice, with a reduced expression of matrix metalloproteinases-9 and aquaporin-4 proteins. Following the reperfusion, the rCBF of the wild-type (WT) mice was quickly restored to the baseline, whereas, in Ent2-/- mice, rCBF was slowly recovered initially, but was then higher than that in the WT mice at the later phase of reperfusion. The improved CMRO2 and reduced ROS level support the beneficial effects caused by the changes in the rCBF of Ent2-/- mice. Further studies showed that the protective effects of Ent2 deletion in mice with tMCAO involve adenosine receptor A2AR. CONCLUSIONS: Ent2 plays a critical role in modulating cerebral collateral circulation and ameliorating pathological events of brain ischemia and reperfusion injury.

The association between exposure to volatile organic compounds and serum lipids in the US adult population.

BACKGROUND AND AIM: Epidemiological evidence on the relationship between exposure to volatile organic compounds (VOCs), both single and mixed, and serum lipid levels is limited, and their relationship remains unclear. Our study aimed to investigate the associations of exposure to VOCs with serum lipid levels in the US adult population. METHODS AND RESULTS: The study examined the association of 16 VOC levels (2-methylhippuric acid, 3- and 4-methylhippuric acid, N-acetyl-S-(2-carbamoylethyl)-L-cysteine, N-acetyl-S-(N-methylcarbamoyl)-L-cysteine, 2-aminothiazoline-4-carboxylic acid, N-acetyl-S-(benzyl)-L-cysteine, N-acetyl-S-(n-propyl)-L-cysteine, N-acetyl-S-(2-carboxyethyl)-L-cysteine, N-acetyl-S-(2-cyanoethyl)-L-cysteine, N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine, N-acetyl-S-(2-hydroxypropyl)-L-cysteine. N-Acetyl-S-(3-hydroxypropyl)-L-cysteine, mandelic acid, N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine, phenylglyoxylic acid and N-acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine) with total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) using data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2015, and a total of 1410 adults were enrolled. The association was evaluated by Bayesian kernel machine regression (BKMR), multiple linear regression and weighted quantile sum (WQS) regression. In BKMR analysis, exposure to VOCs is positively correlated with levels of TC, TG, and LDL-C. However, statistical significance was observed only for the impact on TG. Our linear regression analysis and WQS regression generally support the BKMR results. Several VOCs were positively associated with serum lipid profiles (e.g., the ln-transformed level of mandelic acid (MA) displayed an increase in estimated changes of 7.01 (95% CIs: 2.78, 11.24) mg/dL for TC level), even after the effective number of tests for multiple testing (P < 0.05). CONCLUSIONS: Exposure to VOCs was associated with serum lipids, and more studies are needed to confirm these findings.

Trait emotional intelligence and quality of life among breast cancer patients: The mediating role of fear of cancer recurrence.

BACKGROUND: Trait emotional intelligence and fear of cancer recurrence could predict quality of life, but the mechanism between the three is poorly understood. METHODS: The aim of this study was to investigate the associations between trait emotional intelligence, fear of cancer recurrence and quality of life in patients with breast cancer. A cross-sectional study was conducted with 215 breast cancer patients recruited from two hospitals in China. Data were collected from December 2018 to April 2019. Questionnaires measured demographic and medical characteristics, trait emotional intelligence, fear of cancer recurrence and quality of life. Pearson correlation analysis and structural equation modelling were conducted to analyse the data. RESULTS: As expected, trait emotional intelligence was positively related to quality of life and negatively correlated with fear of cancer recurrence. Fear of cancer recurrence was negatively associated with quality of life. This relationship between trait emotional intelligence and quality of life was mediated by fear of cancer recurrence. CONCLUSIONS: These results shed light on underlying mechanisms by which trait emotional intelligence affects quality of life. Trait emotional intelligence training could reduce fear of cancer recurrence to improve quality of life for cancer patients.

Dectin-2 is a primary receptor for NLRP3 inflammasome activation in dendritic cell response to Histoplasma capsulatum.

Inflammasome is an intracellular protein complex that serves as cytosolic pattern recognition receptor (PRR) to engage with pathogens and to process cytokines of the interleukin-1 (IL-1) family into bioactive molecules. It has been established that interleukin-1ß (IL-1ß) is important to host defense against Histoplasma capsulatum infection. However, the detailed mechanism of how H. capsulatum induces inflammasome activation leading to IL-1ß production has not been studied. Here, we showed in dendritic cells (DCs) that H. capsulatum triggers caspase-1 activation and IL-1ß production through NLRP3 inflammasome. By reciprocal blocking of Dectin-1 or Dectin-2 in single receptor-deficient DCs and cells from Clec4n-/-, Clec7a-/-, and Clec7a-/-Clec4n-/- mice, we discovered that while Dectin-2 operates as a primary receptor, Dectin-1 serves as a secondary one for NLRP3 inflammasome. In addition, both receptors trigger Syk-JNK signal pathway to activate signal 1 (pro-IL-1ß synthesis) and signal 2 (activation of caspase-1). Results of pulmonary infection with H. capsulatum showed that CD103+ DCs are one of the major producers of IL-1ß and Dectin-2 and Dectin-1 double deficiency abolishes their IL-1ß response to the fungus. While K+ efflux and cathepsin B (but not ROS) function as signal 2, viable but not heat-killed H. capsulatum triggers profound lysosomal rupture leading to cathepsin B release. Interestingly, cathepsin B release is regulated by ERK/JNK downstream of Dectin-2 and Dectin-1. Our study demonstrates for the first time the unique roles of Dectin-2 and Dectin-1 in triggering Syk-JNK to activate signal 1 and 2 for H. capsulatum-induced NLRP3 inflammasome activation.

The monocyte-macrophage-mast cell axis in dengue pathogenesis.

Dengue virus, the causative agent of dengue disease which may have hemorrhagic complications, poses a global health threat. Among the numerous target cells for dengue virus in humans are monocytes, macrophages and mast cells which are important regulators of vascular integrity and which undergo dramatic cellular responses after infection by dengue virus. The strategic locations of these three cell types, inside blood vessels (monocytes) or outside blood vessels (macrophages and mast cells) allow them to respond to dengue virus infection with the production of both intracellular and secretory factors which affect virus replication, vascular permeability and/or leukocyte extravasation. Moreover, the expression of Fc receptors on the surface of monocytes, macrophages and mast cells makes them important target cells for antibody-enhanced dengue virus infection which is a major risk factor for severe dengue disease, involving hemorrhage. Collectively, these features of monocytes, macrophages and mast cells contribute to both beneficial and harmful responses of importance to understanding and controlling dengue infection and disease.

Pharmacophore anchor models of flaviviral NS3 proteases lead to drug repurposing for DENV infection.

BACKGROUND: Viruses of the flaviviridae family are responsible for some of the major infectious viral diseases around the world and there is an urgent need for drug development for these diseases. Most of the virtual screening methods in flaviviral drug discovery suffer from a low hit rate, strain-specific efficacy differences, and susceptibility to resistance. It is because they often fail to capture the key pharmacological features of the target active site critical for protein function inhibition. So in our current work, for the flaviviral NS3 protease, we summarized the pharmacophore features at the protease active site as anchors (subsite-moiety interactions). RESULTS: For each of the four flaviviral NS3 proteases (i.e., HCV, DENV, WNV, and JEV), the anchors were obtained and summarized into 'Pharmacophore anchor (PA) models'. To capture the conserved pharmacophore anchors across these proteases, were merged the four PA models. We identified five consensus core anchors (CEH1, CH3, CH7, CV1, CV3) in all PA models, represented as the "Core pharmacophore anchor (CPA) model" and also identified specific anchors unique to the PA models. Our PA/CPA models complied with 89 known NS3 protease inhibitors. Furthermore, we proposed an integrated anchor-based screening method using the anchors from our models for discovering inhibitors. This method was applied on the DENV NS3 protease to screen FDA drugs discovering boceprevir, telaprevir and asunaprevir as promising anti-DENV candidates. Experimental testing against DV2-NGC virus by in-vitro plaque assays showed that asunaprevir and telaprevir inhibited viral replication with EC50 values of 10.4 µM & 24.5 µM respectively. The structure-anchor-activity relationships (SAAR) showed that our PA/CPA model anchors explained the observed in-vitro activities of the candidates. Also, we observed that the CEH1 anchor engagement was critical for the activities of telaprevir and asunaprevir while the extent of inhibitor anchor occupation guided their efficacies. CONCLUSION: These results validate our NS3 protease PA/CPA models, anchors and the integrated anchor-based screening method to be useful in inhibitor discovery and lead optimization, thus accelerating flaviviral drug discovery.

CR3 and Dectin-1 Collaborate in Macrophage Cytokine Response through Association on Lipid Rafts and Activation of Syk-JNK-AP-1 Pathway.

Collaboration between heterogeneous pattern recognition receptors (PRRs) leading to synergistic coordination of immune response is important for the host to fight against invading pathogens. Although complement receptor 3 (CR3) and Dectin-1 are major PRRs to detect fungi, crosstalk between these two receptors in antifungal immunity is largely undefined. Here we took advantage of Histoplasma capsulatum which is known to interact with both CR3 and Dectin-1 and specific particulate ligands to study the collaboration of CR3 and Dectin-1 in macrophage cytokine response. By employing Micro-Western Array (MWA), genetic approach, and pharmacological inhibitors, we demonstrated that CR3 and Dectin-1 act collaboratively to trigger macrophage TNF and IL-6 response through signaling integration at Syk kinase, allowing subsequent enhanced activation of Syk-JNK-AP-1 pathway. Upon engagement, CR3 and Dectin-1 colocalize and form clusters on lipid raft microdomains which serve as a platform facilitating their cooperation in signaling activation and cytokine production. Furthermore, in vivo studies showed that CR3 and Dectin-1 cooperatively participate in host defense against disseminated histoplasmosis and instruct adaptive immune response. Taken together, our findings define the mechanism of receptor crosstalk between CR3 and Dectin-1 and demonstrate the importance of their collaboration in host defense against fungal infection.

Dengue viral protease interaction with NF-κB inhibitor α/ß results in endothelial cell apoptosis and hemorrhage development.

Hemorrhagic manifestations occur frequently accompanying a wide range of dengue disease syndromes. Much work has focused on the contribution of immune factors to the pathogenesis of hemorrhage, but how dengue virus (DENV) participates in the pathogenic process has never been explored. Although there is no consensus that apoptosis is the basis of vascular permeability in human dengue infections, we showed in dengue hemorrhage mouse model that endothelial cell apoptosis is important to hemorrhage development in mice. To explore the molecular basis of the contribution of DENV to endothelial cell death, we show in this study that DENV protease interacts with cellular IκBα and IκBß and cleaves them. By inducing IκBα and IκBß cleavage and IκB kinase activation, DENV protease activates NF-κB, which results in endothelial cell death. Intradermal inoculation of DENV protease packaged in adenovirus-associated virus-9 induces endothelial cell death and dermal hemorrhage in mice. Although the H51 activity site is not involved in the interaction between DENV protease and IκB-α/ß, the enzymatic activity is critical to the ability of DENV protease to induce IκBα and IκBß cleavage and trigger hemorrhage development. Moreover, overexpression of IκBα or IκBß protects endothelial cells from DENV-induced apoptosis. In this study, we show that DENV protease participates in the pathogenesis of dengue hemorrhage and discover IκBα and IκBß to be the new cellular targets that are cleaved by DENV protease.

[Research on life history and phenological period of wild-stimulated cultivated Gastrodia elata f. elata in Guizhou].

In order to get to know the imitation of wild Gastrodia elata in life history and phenology period, by G. elata f. elata forest wild simulated cultivation in Dafang county, Guizhou province, observing and recording its morphological characteristics of each growth and development stage. This experiment summarized the law of its life history over 24 months, amplified the characteristics of each 5 phenology periods over the sexual and asexual reproduction of wild simulated cultivated G. elata f. elata in Guizhou. Which the results could clear the process of wild simulated cultivated G. elata f. elata in Guizhou, and provide a theoretical support for the standard technical of the simulated wild G. elata.

N-ethyl-N-nitrosourea (ENU)-induced C-terminal truncation of Runx3 results in autoimmune colitis associated with Th17/Treg imbalance.

Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory intestinal disease that affects people around the world. The primary cause of IBD is an imbalance in the host immune response to intestinal flora. Several human genes, including IL10, STAT3, IRGM, ATG16L1, NOD2 and RUNX3, are associated with inappropriate immune responses in IBD. It has been reported that homozygous Runx3-knockout (ko) mice spontaneously develop colitis. However, the high mortality rate in these mice within the first two weeks makes it challenging to study the role of Runx3 in colitis. To address this issue, a spontaneous colitis (SC) mouse model carrying a C-terminal truncated form of Runx3 with Tyr319stop point mutation has been generated. After weaning, SC mice developed spontaneous diarrhea and exhibited prominent enlargement of the colon, accompanied by severe inflammatory cell infiltration. Results of immunofluorescence staining showed massive CD4+ T cell infiltration in the inflammatory colon of SC mice. Colonic IL-17A mRNA expression and serum IL-17A level were increased in SC mice. CD4+ T cells from SC mice produced stronger IL-17A than those from wildtype mice in Th17-skewing conditions in vitro. In addition, the percentages of Foxp3+ Treg cells as well as the RORγt+Foxp3+ Treg subset, known for its role in suppressing Th17 response in the gut, were notably lower in colon lamina propria of SC mice than those in WT mice. Furthermore, transfer of total CD4+ T cells from SC mice, but not from wildtype mice, into Rag1-ko host mice resulted in severe autoimmune colitis. In conclusion, the C-terminal truncated Runx3 caused autoimmune colitis associated with Th17/Treg imbalance. The SC mouse model is a feasible approach to investigate the effect of immune response on spontaneous colitis.

Reversible oro-lingual dyskinesia related to lithium intoxication.

PURPOSE: To report the first case of Taiwanese with lithium intoxication presenting as oro-lingual dyskinesia. CASE REPORT: A 68-year-old man had bipolar disorder with chronic lithium treatment. He had acute conscious disturbance, atrial flutter, myoclunus of limbs, and oro-lingual dyskinesia. Biochemistry study revealed elevated blood urea nitrogen, creatinine, and lithium level (3.43 Eq/L). The lithium is discontinued and he received conservational treatment. Along with reduction of serum lithium level, his involuntary movement subsided following by clear consciousness. He had no residual neurological deficit in 3 years of follow up. CONCLUSION: Oro-lingual dyskinesia is a rare presentation of lithium intoxication. This case reminds us such diagnostic possibilities especially in elder patients who receive a chronic lithium therapy.

Cinnamon essential oil vapor alleviates the reduction of aroma-related volatiles in cold-stored "Feicheng" peach using HS-GC-IMS.

"Feicheng" peach is popular for its unique aroma, but its defect of being highly sensitive to chilling injury (CI) often leads to aroma loss and internal browning. Essential oils (EOs) are often used to enhance the antioxidant capacity of plants and fruits, as well as to trigger their defense against biotic/abiotic stresses. This study aimed to examine the effect of cinnamon essential oil (CEO) vapor treatment on the aroma quality of peach fruit during cold storage using HS-GC-IMS. The results showed that 50 µL/L CEO vapor reduced the severity of internal browning (IB) in peaches at the stage of 7 ~ 21 d during refrigeration (Significantly, the L* value was higher and the IB index was lower than that of control, p < 0.05). Meanwhile, the evident reduction or loss of aroma content caused by CI was restored to a higher level than the control (p < 0.05). Furthermore, CEO treatment promoted the release of aroma-related volatiles as evidenced by more propyl acetate, and the dimer of amyl acetate, isoamyl acetate, butyl acetate detected than that on harvest day and no-treated group after 21 d of cold storage plus 2 d of shelf life. Genes of PpLOX1, PpLOX2, PpHPL1 and PpADH1 associated with aroma-related volatile biosynthesis revealed higher transcript abundance in peach fruits treated with CEO than the control (p < 0.05). Overall, our study demonstrated that CEO in vapor phase may be beneficial to alleviate the quality deterioration in aroma and flesh color of "Feicheng" peaches caused by CI, which lays a theoretical reference for maintaining postharvest quality of peach fruits.

False positive detection of serum cryptococcal antigens due to insufficient sample dilution: A case series.

At present, with the development of technology, the detection of cryptococcal antigen (CRAG) plays an increasingly important role in the diagnosis of cryptococcosis. However, the three major CRAG detection technologies, latex agglutination test (LA), lateral flow assay (LFA) and Enzyme-linked Immunosorbent Assay, have certain limitations. Although these techniques do not often lead to false-positive results, once this result occurs in a particular group of patients (such as human immunodeficiency virus patients), it might lead to severe consequences. CASE SUMMARY: In the three cases we reported, we found that insufficient dilution of the samples may lead to false-positive results in the detection of cryptococcal capsule antigen, which has never been reported before. CONCLUSION: Therefore, once the test results are inconsistent with the clinical symptoms, it is necessary to reexamine the samples carefully. Especially for LFA and LA, the samples can be fully diluted or segmented diluted to avoid false-positive results. It is certain that in the diagnosis, fluid and tissue culture should also be improved, combined with imaging, ink staining, and other methods to improve the accuracy of the diagnosis further.

[Effects of quercetin on nuclear factor-κB p65 expression in renal ubiquitin-proteasome system of diabetic rats].

OBJECTIVE: To investigate the protective effect of quercetin on diabetic nephropathy and to explore its possible mechanism. METHODS: Type 2 diabetes mellitus rat model was established by feeding high-carbohydrate-fat diet and injecting with streptozotocin. At 72 hour after injection, blood samples were collected from the tail veins of all rats. Those rats with blood glucose level ≥ 16.7 mmol/L were considered as the diabetes model been successfully established. The model rats were randomly divided into type 2 diabetic group (group DM, n = 9) and quercetin group (group QUE, n = 9). Other rats were used as normal controls (group NC, n = 8). All rats were performed by intragastric administration for 8 weeks. At the end of experiment, the rats were sacrificed and fasting plasma glucose (FPG), fasting insulin(FIns), serum creatinine (SCr), blood urea nitrogen (BUN), TG, TC, LDL-C, 24 h urine protein (24 h UP), and kidney index (KI) were evaluated. Pathological changes of kidney were observed by periodic acid-silver methenamine (PASM). The expressions of ubiquitin and NF-κB p65 on glomeruli were examined by immunohistochemical method, and its association with the incidence of proteinuria was analyzed. RESULTS: In groups DM and QUE, the level of FPG [(25.45 ± 1.23) mmol/L and (19.99 ± 1.20) mmol/L], FIns [(25.67 ± 2.58) mU/L and (19.29 ± 1.80) mU/L], SCr [(44.00 ± 2.53) µmol/L and (34.43 ± 2.23) µmol/L], BUN[(11.60 ± 0.39) mmol/L and (8.20 ± 0.37) mmol/L], TG[(3.32 ± 0.22)mmol/L and (2.43 ± 0.25) mmol/L], TC [(2.95 ± 0.21) mmol/L and (2.24 ± 0.17) mmol/L], LDL-C [(2.03 ± 0.22) mmol/L and (1.49 ± 0.13) mmol/L], 24 h UP[(46.67 ± 2.50) mg/24 h and (25.57 ± 2.82) mg/24 h] and KI [(9.76 ± 0.30)×10³ and (8.44 ± 0.26)×10³] were significantly increased than the indexes of group NC [(6.56 ± 0.41) mmol/L, (12.63 ± 1.41) mU/L, (22.88 ± 2.36) µmol/L, (5.45 ± 0.51) mmol/L, (1.64 ± 0.11) mmol/L, (1.33 ± 0.17) mmol/L, (0.46 ± 0.05) mmol/L, (12.38 ± 1.19)/24 h and (6.78 ± 0.12)×10³]. Moreover, the above indexes in group QUE were obviously lower than group DM. There was evidence of pathological changes associated with diabetes, such as focal and segmental sclerosis and thickened basement and mesangial expansion. The expressions of ubiquitin and NF-κB p65 in renal tissues of group DM increased significantly (P < 0.01). The expression of ubiquitin and NF-κB p65 were positively related with the level of 24 h UP (r = 0.893, 0.879, P < 0.01). Compared with group DM, all above indexes in group QUE were markedly alleviated (P < 0.01). The expression of ubiquitin and NF-κB p65 was reduced but didn't reach level in group NC (P < 0.01). CONCLUSION: The increased expression of NF-κB induced by ubiquitin-proteasome system may participate in the pathogenesis of proteinuria in diabetic nephropathy. Quercetin has renal protective effects partly through reducing NF-κB p65 expression.

The bidirectional relationship between metabolic syndrome and hyperuricemia in China: A longitudinal study from CHARLS.

OBJECTIVE: It has been reported that metabolic syndrome (MetS) has been associated with hyperuricemia. However, current findings have been inconclusive regarding the direction of this association. The objective of this study was to clarify the possible directional relationship between hyperuricemia and MetS. DESIGN: This study used two waves of data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011 and 2015 (N = 6,253, aged ≥40 years). Logistic regression and cross-lagged panel design were performed to evaluate the bidirectional association between uric acid with MetS. MetS score is defined as the number of MetS components present. RESULTS: New-onset hyperuricemia and MetS were observed in a four-year follow-up study among 719 and 625 participants, respectively. A positive association was observed in the adjusted logistical regression model between baseline MetS score and new-onset hyperuricemia (P for trend <0.001), and also between baseline serum uric acid (SUA) and new-onset MetS (P for trend <0.001). Cross-lagged panel analysis indicated MetS score positively and prospectively predicted SUA, but not vice versa. After stratification by sex, we observed a strong, bidirectional relationship between MetS score and SUA indicating that diagnosis in one illness increased the risk of the other, both men and women. Moreover, this study also found that systolic blood pressure (P < 0.001) and triglycerides (P < 0.001) had a bidirectional relationship with SUA. CONCLUSIONS: The results of this study indicated a bidirectional relationship between MetS and hyperuricemia.

Effects of flash glucose monitoring on glycemic control in participants with diabetes mellitus: A meta-analysis of randomized controlled trials.

BACKGROUND: With the introduction of flash glucose monitoring (FGM) into the international market in 2014, academics worldwide are exploring whether this device improves glycemic control in participants with diabetes mellitus. OBJECTIVE: A study was conducted in which participants were evaluated to determine the effect of FGM on glycemic control. METHODS: From inception to April 9, 2022, we searched the Cochrane Library, PubMed, SinoMed, Embase, Web of Science, MEDLINE, CNKI, Wan Fang Data, and VIP databases to collect randomized controlled trials (RCTs) related to the effect of FGM on glycemic control in participants with diabetes mellitus. Outcomes included glycated hemoglobin, the occurrence of hypoglycemic events, fasting plasma glucose (FPG), and 2-h postprandial glucose (2hPG) levels. The statistical analysis was performed using R 4.1.3 software. RESULTS: We included 19 studies involving 2013 participants, all of which were RCTs. Meta-analysis results revealed that compared to self-monitoring of blood glucose (SMBG), FGM significantly reduced glycated hemoglobin levels in participants with type 2 diabetes mellitus [mean difference = -0.74 [95 % CI-1.16, -0.32], P < 0.01] and type 1 diabetes mellitus combined with type 2 diabetes mellitus [mean difference = -1.14 [95 % CI-3.14, 0.87], P < 0.01], with a greater effect in participants aged ≤65 years with type 2 diabetes mellitus (mean difference = -1.38 [95 % CI-2.05, -0.72], P < 0.01). However, there was no effect of FGM on the improvement of glycated hemoglobin levels in patients with type 1 diabetes mellitus [P = 0.45]. Furthermore, fasting plasma glucose levels and 2-h postprandial glucose levels were significantly lower in FGM than SMBG, and the number of hypoglycemic events was also significantly lower. CONCLUSION: Comparing SMBG with FGM indicated that FGM improves fasting plasma glucose levels, 2-h postprandial glucose levels, and glycated hemoglobin levels, and it reduces the number of hypoglycemic events.

Non-alcoholic Wernicke encephalopathy in an esophageal cancer patient receiving radiotherapy: A case report.

BACKGROUND: Wernicke encephalopathy is a rare but potentially fatal adverse event caused by thiamine deficiency. Reports of non-alcoholic Wernicke encephalopathy due to malignancy are scarce in the literature, with those reported mainly being on haematological cancer, followed by gastrointestinal cancer. As a result, there is considerable under-recognition and delay in the diagnosis and treatment of Wernicke encephalopathy in oncology departments. To our knowledge, there has been no report of Wernicke encephalopathy in a patient with esophageal cancer while receiving radiotherapy. CASE SUMMARY: A 64-year-old man presented to the oncology outpatient clinic with a history of dysphagia for 2 mo, and was diagnosed with locally advanced esophageal squamous cell carcinoma (stage IIIB). Radiotherapy was initiated to alleviate dysphagia due to malignant esophageal stenosis; however, the patient exhibited consciousness disturbances starting on day 10 of radiotherapy. Brain magnetic resonance imaging indicated the development of Wernicke encephalopathy. Subsequent treatment with thiamine led to rapid improvement in the patient's neurological symptoms. CONCLUSION: Wernicke encephalopathy may develop in non-alcoholic patients undergoing radiotherapy for esophageal cancer. Early diagnosis and sufficient thiamine supplementation during radiotherapy are essential.

Mortality in patients with COVID-19 requiring extracorporeal membrane oxygenation: A meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic and significant public health issue. The effectiveness of extracorporeal membrane oxygenation (ECMO) in treating COVID-19 patients has been called into question. AIM: To conduct a meta-analysis on the mortality of COVID-19 patients who require ECMO. METHODS: This analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes 2020 (PRISMA) and has been registered at the International Prospective Register of Systematic Reviews (number CRD42020227414). A quality assessment for all the included articles was performed by the Newcastle-Ottawa Scale (NOS). Studies with tenor more COVID-19 patients undergoing ECMO were included. The random-effects model was used to obtain the pooled incidence of mortality in COVID-19 patients receiving ECMO. The source of heterogeneity was investigated using subgroup and sensitivity analyses. RESULTS: We identified 18 articles with 1494 COVID-19 patients who were receiving ECMO. The score of the quality assessment ranged from 5 to 8 on the NOS. The majority of patients received veno-venous ECMO (93.7%). Overall mortality was estimated to be 0.31 [95% confidence interval (CI): 0.24-0.39; I 2 = 84.8%] based on random-effect pooled estimates. There were significant differences in mortality between location groups (33.0% vs 55.0% vs 37.0% vs 18.0%, P < 0.001), setting groups (28.0% vs 34.0%, P < 0.001), sample size (37.0% vs 31.0%, P < 0.001), and NOS groups (39.0% vs 19.0%, P < 0.001). However, both subgroup analyses based on location, setting, and sample size, and sensitivity analysis failed to identify the source of heterogeneity. The funnel plot indicated no evident asymmetry, and the Egger's (P = 0.95) and Begg's (P = 0.14) tests also revealed no significant publication bias. CONCLUSION: With more resource assessment and risk-benefit analysis, our data reveal that ECMO might be a feasible and effective treatment for COVID-19 patients.

The association between hearing threshold and urinary personal care and consumer product metabolites in middle-aged and elderly people from the USA.

Endocrine disruptors have been reported to be associated with hearing ability. However, the association between personal care and consumer product chemicals, known as commonly detected endocrine disruptors, and age-related hearing loss still remains unclear. This study aimed to examine the association between exposure to 7 personal care and consumer product chemicals and hearing thresholds in middle-aged and elderly people. A nationally representative cross-sectional study was performed. Eight hundred forty-five adults aged over 45 from the National Health and Nutrition Examination Survey (NHANES) were included in this study. Bayesian kernel machine regression (BKMR) and the k-medoid cluster analysis were used to evaluate the mixture effect of exposure to 7 chemicals on pure-tone average (PTA). Exposure to these chemicals was negatively associated with PTA. 2,5-Dichlorophenol had the greatest contribution to the mixture effect. The mixture effect was stronger in women, elderly people. Four pooled clusters were identified according to 7 chemicals exposures. Cluster 4 (high TCS exposure) showed a lower HFPTA (P = 0.00258) than cluster 3 (the lowest exposure cluster, as a reference). Our study provides evidence that exposure to personal care and consumer product chemicals might be inversely associated with PTA. More studies are needed to fully understand the association of exposure to these chemicals with hearing threshold.