Antibiotic Exposure and Risk of New-Onset Inflammatory Bowel Disease: A Systematic Review and Dose-Response Meta-Analysis.

BACKGROUND & AIMS: The association between antibiotic exposure and inflammatory bowel disease (IBD) remains controversial, especially whether there is a dose-response relationship. We aimed to conduct a systematic review and meta-analysis to thoroughly evaluate the risk of new-onset IBD associated with antibiotic exposure. METHODS: Four databases were searched from their inception to September 30, 2023 for all relevant studies. The risk estimates were pooled together using random-effects models, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, stratified by IBD subtype, age, exposure period, study type, and antibiotic classes. Dose-response relationship between the number of antibiotic prescriptions and IBD risk was assessed using generalized least squares regression analysis. RESULTS: Twenty-eight studies involving 153,027 patients with IBD were included. Antibiotic exposure was significantly associated with an increased risk of new-onset IBD for prescription-based studies (pooled OR, 1.41; 95% CI, 1.29-1.53) and for questionnaire-based studies (pooled OR, 1.35; 95% CI, 1.08-1.68). This association existed for both Crohn's disease and ulcerative colitis, as well as in children and adults for prescription-based studies. The majority of antibiotic classes were associated with an increased IBD risk, with metronidazole (OR, 1.70; 95% CI, 1.38-2.10) and quinolones (OR, 1.56; 95% CI, 1.37-1.77) having relatively higher risk estimates. A positive nonlinear dose-response association was observed between the number of antibiotic prescriptions and IBD risk. CONCLUSIONS: Antibiotic exposure was significantly associated with an increased risk of new-onset IBD, and a positive nonlinear dose-response relationship was observed. Antibiotic stewardship may be important for reducing IBD risk.

Hydroxyl-Decorated Carbon Cloth with High Potassium Affinity Enables Stable Potassium Metal Anodes.

Highly anticipated potassium metal batteries possess abundant potassium reserves and high theoretical capacity but currently suffer from poor cycling stability as a result of dendritic growth and volume expansion. Here, carbon cloths modified with different functional groups treated with ethylene glycol, ethanolamine, and ethylenediamine are designed as 3D hosts, exhibiting different wettability to molten potassium. Among them, the hydroxyl-decorated carbon cloth with a high affinity for potassium can achieve molten potassium perfusion (K@EG-CC) within 3 s. By efficiently inducing the uniform deposition of metal potassium, buffing its volume expansion, and lowering local current density, the developed K@EG-CC anode alleviates the dendrite growth issue. The K@EG-CC||K@EG-CC symmetric battery can be cycled stably for 2100 h and has only a small voltage hysteresis of ≈93 mV at 0.5 mA cm-2 . Moreover, the high-voltage plateau, high energy density, and long cycle life of K metal full batteries can be realized with a low-cost KFeSO4 F@carbon nanotube cathode. This study provides a simple strategy to promote the commercial applications of potassium metal batteries.

Fecal Coprococcus, hidden behind abdominal symptoms in patients with small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals. METHODS: To explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing. RESULTS: Fecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO. CONCLUSIONS: This study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus's abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT's complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.

Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.

BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.

KI-Assisted Formation of Spindle-like Prussian White Nanoparticles for High-Performance Potassium-Ion Battery Cathodes.

Prussian white (PW) is considered as a promising cathode material for potassium-ion batteries (KIBs) due to its low cost and high theoretical capacity. However, the high water content and structural defects and the strict synthesis conditions of PW lead to its unsatisfactory cycling performance and low specific capacity, hindering its practical applications. Herein, a template-engaged reduction method is proposed, using MIL-88B(Fe) as a self-template and KI as the reducing agent to prepare K-rich PW with low defects and water content. Furthermore, the hierarchical porous spindle-like morphology can be inherited from the precursor, furnishing sufficient active sites and reducing the ion diffusion path. Consequently, when applied as a KIB cathode material, spindle-like PW (K1.72Fe[Fe(CN)6]0.96·0.342H2O) manifested remarkable potassium storage properties. Notably, a full cell assembled by the spindle-like PW cathode and graphite anode exhibited a large energy density of ∼216.7 Wh kg-1, demonstrating its huge potential for energy storage systems.

Uniform P2-K0.6CoO2 Microcubes as a High-Energy Cathode Material for Potassium-Ion Batteries.

Layered transition-metal (TM) oxides have drawn ever-growing interest as positive electrode materials in potassium-ion batteries (PIBs). Nevertheless, the practical implementation of these positive electrode materials is seriously hampered by their inferior cyclic property and rate performance. Reported here is a self-templating strategy to prepare homogeneous P2-K0.6CoO2 (KCO) microcubes. Benefiting from the unusual microcube architecture, the interface between the electrolyte and the active material is considerably diminished. As a result, the KCO microcubes manifest boosted electrochemical properties for potassium storage including large reversible capacity (87.2 mAh g-1 under 20 mA g-1), superior rate performance, and ultralong cyclic steady (an improved capacity retention of 86.9% under 40 mA g-1 after 1000 cycles). More importantly, the fabrication approach can be effectively extended to prepare other layered TM oxide (P3-K0.5MnO2, P3-K0.5Mn0.8Fe0.2O2, P2-K0.6Co0.67Mn0.33O2, and P2-K0.6Co0.66Mn0.17Ni0.17O2) microcubes and nonlayered TM oxide (KFeO2) microcubes.

Tunable Interfacial Electric Field-Mediated Cobalt-Doped FeSe/Fe3Se4 Heterostructure for High-Efficiency Potassium Storage.

The interfacial electric field (IEF) in the heterostructure can accelerate electron transport and ion migration, thereby enhancing the electrochemical performance of potassium-ion batteries (PIBs). Nevertheless, the quantification and modulation of the IEF for high-efficiency PIB anodes currently remains a blank slate. Herein, we achieve for the first time the quantification and tuning of IEF via amorphous carbon-coated undifferentiated cobalt-doped FeSe/Fe3Se4 heterostructure (denoted UN-CoFe4Se5/C) for efficient potassium storage. Co doping can increase the IEF in FeSe/Fe3Se4, thereby improving the electron transport, promoting the potassium adsorption capacity, and lowering the diffusion barrier. As expected, the IEF magnitude in UN-CoFe4Se5/C is experimentally quantified as 62.84 mV, which is 3.65 times larger than that of amorphous carbon-coated FeSe/Fe3Se4 heterostructure (Fe4Se5/C). Benefiting from the strong IEF, UN-CoFe4Se5/C as a PIB anode exhibits superior rate capability (145.8 mAh g-1 at 10.0 A g-1) and long cycle lifespan (capacity retention of 95.1 % over 3000 cycles at 1.0 A g-1). Furthermore, this undifferentiated doping strategy can universally regulate the IEF magnitude in CoSe2/Co9Se8 and FeS2/Fe7S8 heterostructures. This work can provide fundamental insights into the design of advanced PIB electrodes.

A P2/P3 Biphasic Layered Oxide Composite as a High-Energy and Long-Cycle-Life Cathode for Potassium-Ion Batteries.

Layered transition metal oxides are extensively considered as appealing cathode candidates for potassium-ion batteries (PIBs) due to their abundant raw materials and low cost, but their further implementations are limited by slow dynamics and impoverished structural stability. Herein, a layered composite having a P2 and P3 symbiotic structure is designed and synthesized to realize PIBs with large energy density and long-term cycling stability. The unique intergrowth of P2 and P3 phases in the obtained layered oxide is plainly characterized by X-ray diffraction refinement, high-angle annular dark field and annular bright field-scanning transmission electron microscopy at atomic resolution, and Fourier transformation images. The synergistic effect of the two phases of this layered P2/P3 composite is well demonstrated in K+ intercalation/extraction process. The as-prepared layered composite can present a large discharge capacity with the remarkable energy density of 321 Wh kg-1 and also manifest excellent capacity preservation after 600 cycles of K+ uptake/removal.

Incidence of Inflammatory Bowel Disease in Urban China: A Nationwide Population-based Study.

BACKGROUND & AIMS: Limited studies have evaluated the burden of inflammatory bowel disease (IBD) in China. We aimed to estimate the incidence of IBD including ulcerative colitis (UC) and Crohn's disease (CD) in urban China. METHODS: The national urban incidence in 2016 was calculated based on urban basic medical insurance from 2012 to 2016 in China by using a 4-year washout period. The incidence in Yinzhou District estimated from the Yinzhou electronic health care record database was used to test the accuracy of the results from insurance data. RESULTS: A total of 95,555 patients with IBD were identified. The incidence in 2016 was 10.04 (95% confidence interval, 6.95-13.71) per 100,000 person-years. The incidence rates of both UC and CD were higher among males than among females. There was a sharp increase in UC incidence before the age of 30 years and stabilization in later years (50-79 years old), whereas CD incidence peaked at 30 to 34 years old and experienced decline subsequently. The incidence of UC was much greater than that of CD, with a UC-to-CD incidence ratio of 12.61. The results from the Yinzhou database confirmed these results. CONCLUSIONS: This study is the first to draw a portrait of the distribution of IBD in urban China. The difference in IBD incidence between urban China and other countries suggests an association between the IBD burden and industrialization process. The accelerating urbanization and industrialization process in China, a country with a population of 1.4 billion people, will likely increase the burden of IBD.

Phase Separation in cGAS-STING Signaling: Cytosolic DNA Sensing and Regulatory Functions.

Phase separation is a crucial biophysical process that governs cellular signaling and function. This process allows biomolecules to separate and form membraneless compartments in response to both extra- and intra-cellular stimuli. Recently, the identification of phase separation in different immune signaling pathways, including the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, has shed light on its tight association with pathological processes such as viral infections, cancers, and inflammatory diseases. In this review, we present the phase separation in cGAS-STING signaling, along with its related cellular regulatory functions. Furthermore, we discuss the introduction of therapeutics targeting cGAS-STING signaling, which plays a pivotal role in cancer progression.

Absence of NOTCH1 mutation and presence of CDKN2A deletion predict progression of esophageal lesions.

Currently, surveillance for esophageal squamous cell carcinoma (ESCC) runs a risk of underestimation of early lesions which show absence of iodine staining, with no or only mild histologic changes. The development of molecular markers that indicate risk of progression is thus warranted. We performed whole-exome sequencing on biopsies from two sequential endoscopies of a single esophageal lesion and matching blood samples. There were 27 pairs of age-, gender-, pathologic stage-, and sampling interval-matched progressors and non-progressors identified in a prospective community-based ESCC screening trial. Putative molecular progression markers for ESCC were first evaluated by comparing somatic mutation, copy number alteration (CNA), and mutational signature information among progressors and non-progressors. These markers were then validated with another 24 pairs of matched progressors and non-progressors from the same population using gene alteration status identified by target sequencing and quantitative PCR. Progressors had more somatic mutation and CNA burden, as well as apolipoprotein B mRNA editing catalytic polypeptide-like and age-related signature weights compared with non-progressors. A gene score consisting of somatic NOTCH1 mutation and CDKN2A deletion is predictive of risk of progression in lesions which show absence of iodine staining under endoscopy but have no or only mild dysplasia. This gene score was also validated in an external cohort of matched progressors and non-progressors. Absence of NOTCH1 mutation and presence of CDKN2A deletion are markers of progression in squamous lesions of the esophagus. This gene score would be an ideal indicator for assisting the pathologist in the identification of high-risk individuals who could be potentially 'missed' or subject to a risk underestimation by histologic analysis, and might improve the performance of ESCC surveillance. © 2022 The Pathological Society of Great Britain and Ireland.

Multiple Lugol-unstained lesions predict higher cumulative risk of malignance in the esophagus.

BACKGROUND AND AIM: The impact of the presence of multiple Lugol-unstained lesions (LULs) in the esophagus on the risk of having severe dysplasia and above (SDA) lesions among asymptomatic individuals is unknown. METHODS: We collected demographic factors, behavioral variables, and features of LULs from 1073 participants who were biopsied at baseline endoscopic screening in a population-based screening trial, and these individuals were followed over a median time of 7 years. Outcome events were defined as SDA identified at screening, at reexamination, or during follow-up. "Multiple LULs" were defined as ≥ 2 LULs found in the entirety of the esophagus. Multivariable logistic regression models were fitted to assess the effect of "multiple LULs" on the cumulative risk of SDA. RESULTS: There were 147 SDA cases in the current study. After adjustment for potential risk factors and endoscopic features of LULs, the presence of "multiple LULs" slightly increased the cumulative risk of having SDA with no statistical significance (adjusted odds ratio [OR] = 1.26; 95% confidence interval [CI] [0.85, 1.88]). Further stratified analysis showed that this association was strong among subjects with small LULs (≤ 5 mm) (adjusted OR = 3.29; 95% CI [1.39, 7.79]). However, no such association was observed in subjects with larger LULs (adjusted OR = 0.99; 95% CI [0.63, 1.55], P interaction  = 0.022). CONCLUSIONS: The presence of "multiple small LULs (≤ 5 mm)" in chromoendoscopy indicates a higher cumulative risk of having SDA in the esophagus. We recommend biopsies be taken and surveillance be maintained at a more active level in individuals with relatively small but multiple LULs.

Lugol-unstained lesions location in the esophagus affects the detection rate of malignancy: a population-based study.

INTRODUCTION: This study aimed to evaluate the impact of Lugol-unstained lesion (LUL) location on the detection yield, which may help the endoscopist select targets for biopsy. METHODS: We enrolled 1064 subjects who had LULs at the baseline screening of a population-based randomized controlled trial. There were 1166 LULs with recorded location and pathologic diagnosis, and these were used for analysis. The detection rate of severe dysplasia and above (SDA) was calculated as the number of LULs identified as SDA divided by the number of LULs biopsied. Logistic regression with a generalized estimating equation was applied to evaluate the association between the location of a given LUL and the risk of the LUL being SDA. RESULTS: The detection rate of SDA for LULs located in the lower, middle, and upper esophagus increased from 5.9% and 10.9% to 16.7%. LUL location was significantly associated with having SDA (adjusted odds ratio (OR)upper vs. lower  = 2.88, 95% confidential interval (CI) = 1.48-5.60; adjusted ORmiddle vs. lower  = 1.63, 95% CI = 0.96-2.76), and the association was stronger in subgroups with a family history of esophageal squamous cell carcinoma (ESCC) (adjusted ORupper vs. lower  = 9.72, 95% CI = 2.57-36.69; adjusted ORmiddle vs. lower  = 3.76, 95% CI = 0.93-15.21). CONCLUSIONS: Our results suggest that more attention should be paid by endoscopists to LULs in the upper and middle esophagus, particularly for individuals with a family history of ESCC.

Prunolactones A-G, proangiogenic isocoumarin derivatives with an unusual 6/6/6/6/6 spiropentacyclic skeleton from the endophytic fungus Phomopsis prunorum.

Seven novel isocoumarins, prunolactones A-G (1-7), featuring an unusual 6/6/6/6/6 spiropentacyclic skeleton, together with two biosynthetic precursors phomopsilactone (8) and methyl 3-epi-shikimate (9), were isolated from the endophytic fungus Phomopsis prunorum guided by UPLC-QTOF-MS and 1H NMR spectroscopic analytical techniques. Their structures including absolute configurations of 1-7 were elucidated based on extensive spectroscopic data, X-ray diffraction analysis, and ECD calculations. Biogenetically, compounds 1-7 are proposed to be derived from polyketide and shikimate pathways via key intermolecular Diels - Alder reactions. Compounds 2, 3, and 7 showed significant in vivo proangiogenic activity in transgenic zebrafish.

Xenon-lamp simulated sunlight-induced photolysis of pyriclobenzuron in water: Kinetics, degradation pathways, and identification of photolysis products.

Pyriclobenzuron 1(PBU) is a novel molluscicide developed to control Pomacea canaliculate, and little information on its environmental fate has been published. In this study, the photolysis of PBU in an aqueous environment was simulated using a xenon lamp. Results showed that the photolysis of PBU in water followed first-order kinetics, exhibiting a t0.5 of 95.1 h and 83.6 h in Milli-Q water and river water, respectively. Two main photolysis products 2(PPs) were detected by HPLC-UV and identified by UPLC-Q/TOF MS, which were formed via the hydroxylation and photocatalytic hydro-dehalogenation of PBU, respectively. The initial relative abundance of photolysis product 1 3(PP-1) in Milli-Q water was 1.55 times higher than that in river water. PP-1 was detected at 26.5 % and 76.8 % of the maximum relative abundance in the river water and Milli-Q water after 720 h, respectively. Photolysis product 2 4(PP-2) was stable in water because of its weak hydrophilicity. The PP-2 detected after 720 h in Milli-Q water and river water was 93.7 % and 93.5 % of the maximum relative abundance, respectively. Finally, ECOSAR software was used to evaluate the acute aquatic toxicity of PBU and its PPs, revealing that the PPs had lower toxicity levels to non-target aquatic organisms.

Layered Oxide Cathodes Promoted by Crystal Regulation Strategies for Potassium-Ion Batteries.

Layered oxide cathodes have demonstrated great potential for potassium-ion batteries (PIBs) on account of high reversible capacity, appropriate diffusion paths, and low cost. However, their electrochemical performance in PIBs is generally worse than that in lithium-ion batteries due to large structural changes and deformations during charging and discharging. To improve their potassium storage performance, a series of strategies have been developed in recent studies. In this review, we summarize the latest advancements in layered oxide cathodes for PIBs through different crystal regulation strategies, including transition metal layer doping, potassium content optimization, oxygen partial substitution, functional morphology construction and air stability improvement. Meanwhile, the relationship between the electrochemical properties and structural evolution of these modified cathodes is also investigated. In addition, the challenges and prospects of these layered oxide cathodes in PIBs are analyzed in detail, providing constructive insights for future applications of PIBs.

Telemedicine and Clinical Outcomes in Peritoneal Dialysis: A Propensity-Matched Study.

INTRODUCTION: Telemedicine (TM) has shown to provide potential benefits on clinical outcomes in patients with chronic kidney disease but limited evidences published in the peritoneal dialysis (PD) population. This study aimed to explore the long-term effects of TM on the mortality and technique failure. METHODS: The Peritoneal Dialysis Telemedicine-assisted Platform Cohort Study (PDTAP Study) was conducted prospectively in 27 hospitals in China since 2016. Patient and practice data were collected through the doctor-end of the TM app (Manburs) for all participants. TM including self-monitoring records, on-line education materials, and real-time physician-patient contact was only performed for the patient-end users of the Manburs. The primary outcome was all-cause mortality. The secondary outcomes were cause-specific mortality and all-cause and cause-specific permanent transfer to hemodialysis. RESULTS: A total of 7,539 PD patients were enrolled between June 2016 and April 2019, with follow-up till December 2020. Patients were divided into two cohorts: TM group (39.1%) and non-TM group (60.9%). A propensity score was used to create 2,160 matched pairs in which the baseline covariates were well-balanced. There were significantly lower risks of all-cause mortality (HR 0.59 [0.51, 0.67], p < 0.001), CVD mortality (HR 0.59 [0.49, 0.70], p < 0.001), all-cause transfer to hemodialysis (0.57 [0.48, 0.67], p < 0.001), transfer to hemodialysis from PD-related infection (0.67 [0.51, 0.88], p = 0.003), severe fluid overload (0.40 [0.30, 0.55], p < 0.001), inadequate solute clearance (0.49 [0.26, 0.92], p = 0.026), and catheter-related noninfectious complications (0.41 [0.17, 0.97], p = 0.041) in the TM group compared with the non-TM group. CONCLUSION: This study indicated real-world associations between TM usage and reduction in patient survival and technique survival through a multicenter prospective cohort.

The role of microbiota-mitochondria crosstalk in pathogenesis and therapy of intestinal diseases.

The interaction between mitochondria and gut microbiota plays a critical role in intestinal physiological homeostasis. In this kind of homeostasis, intestinal epithelial hypoxia helps microbiota to be dominated by obligate anaerobes, who provide their benefit metabolites for the host, such as short chain fatty acids (SCFAs). In addition, emerging studies suggest that microbial signals to the mitochondria of intestinal epithelial cells (IECs) could alter mitochondrial ultrastructure and its metabolic function, induce inflammasome activation and disrupt epithelial hypoxia. Conditions that alter the mitochondria could lead to intestinal epithelium inflammation and oxygenation, both of which would drive an expansion of facultative anaerobes and exacerbate the imbalance of mitochondria-microbiota crosstalk. This phenomenon has proved to be associated with the pathogenesis of gastrointestinal (GI) diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). Therefore, in this review, we summarized the recent process on the interaction between mitochondria of IECs and gut microbiota in the case of both GI physiological homeostasis and diseases, and potential therapeutic interventions targeting mitochondria-microbiota crosstalk in GI diseases.

Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine.

BACKGROUND: Cystic echinococcosis (CE) is a life-threatening zoonosis caused by the larval form of Echinococcus granulosus tapeworm. Our previous study showed that an approved drug pyronaridine (PND) is highly effective against CE, both in vitro and in an animal model. To identify possible target genes, transcriptome analysis was performed with E. granulosus sensu stricto protoscoleces treated with PND. RESULTS: A total of 1,321 genes were differentially expressed in protoscoleces treated with PND, including 541 upregulated and 780 downregulated genes. Gene ontology and KEGG analyses revealed that the spliceosome, mitogen-activated protein kinase (MAPK) pathway and ATP-binding cassette (ABC) transporters were the top three enriched pathways. Western blot analysis showed that PND treatment resulted in a dose-dependent increase in protein expression levels of EgMKK1 (MKK3/6-like) and EgMKK2 (MEK1/2-like), two members of MAPK cascades. Interestingly, several heat shock protein (HSP) genes were greatly downregulated including stress-inducible HSPs and their constitutive cognates, and some of them belong to Echinococcus-specific expansion of HSP70. CONCLUSIONS: PND has a great impact on the spliceosome, MAPK pathway and ABC transporters, which may underline the mechanisms by which PND kills E. granulosus protoscoleces. In addition, PND downregulates HSPs expression, suggesting a close relationship between the drug and HSPs.

Size of Lugol-unstained lesions as a predictor for risk of progression in premalignant lesions of the esophagus.

BACKGROUND AND AIMS: At present, the surveillance strategy for premalignant esophageal lesions in China is based solely on the pathologic diagnosis in Lugol's chromoendoscopy (LCE). In this study, we sought to determine the degree to which various unstained features under LCE may lead to improved ability to predict the risk of progression in esophageal lesions. METHODS: We re-examined and followed up on 1058 subjects who had Lugol-unstained lesions (LULs) together with a pathologic diagnosis that was lower than severe dysplasia at baseline screening based on a population-based randomized controlled trial over a median time of 5.8 years. We established a logistic regression model and calculated the adjusted cumulative incidence of severe dysplasia or malignancy. RESULTS: LUL size was predictive of progression to malignant lesions in individuals with a nondysplastic diagnosis (adjusted odd ratio6-10 mm vs ≤5 mm, 6.7; 95% confidence interval, 1.7-25.7; adjusted odds ratio>10 mm vs ≤5 mm, 27.9; 95% confidence interval, 7.3-105.7), and the corresponding adjusted cumulative incidence of malignant lesions was 3.6 and 13.2 per 100 persons. This is higher than that of small (≤5 mm) lesions, which showed mild dysplasia (2.7 per 100 persons), a condition for which surveillance every 3 years is recommended. Under the current approach, 65.3% of interval cancers missed at surveillance would be detected if individuals with medium (6-10 mm) and large (>10 mm) nondysplastic LULs were additionally monitored. CONCLUSIONS: We propose a modified surveillance strategy that combines findings under LCE examination and the pathologic analysis, where follow-up endoscopy is recommended for individuals with relatively large nondysplastic lesions.