Search

Immune checkpoint inhibitors, a type of immunotherapy, have demonstrated optimal treatment efficacy in inducing durable antitumor responses in various cancers. Cytokine-release syndrome is a rare immune-related adverse event induced by immune checkpoint inhibitors. In our case, a patient with hypopharyngeal squamous cell carcinoma received toripalimab combined with chemotherapy. On the fourth day post treatment, the patient developed fever and hypotension. Laboratory examination indicated myelosuppression, acute kidney injury and disseminated intravascular coagulation. Meanwhile, serum cytokine levels of IL-6, IL-8, IL-10, IL-1β, IFN-γ and the level of hypersensitive C-reactive protein were markedly elevated. The patient was diagnosed with cytokine release syndrome, which progressed rapidly and led to the patient’s demise on the fifth day post treatment.

At present, in the evaluation of iron tailings resources, the single evaluation of a certain aspect is limited to the qualitative evaluation, and there is no uniform standard in either theory or method. In this paper, based on the grey group analytic hierarchy process and fuzzy mathematics as the analysis tool, the benefit of the iron tailings resources is analyzed, From resource benefit, economic benefit, environmental benefit and social benefit several aspects to build the differential - efficiency index system and established the differential-benefit evaluation model and the influence of iron tailings resource evaluation of the weight of each index distribution, is obtained by correlation analysis and the likelihood of benefit index influencing the size of the order, to a certain extent, verified the rationality of the index weight, provides a theoretical guidance for iron tailings resource utilization.

To update the evidence of anti-müllerian hormone (AMH) as predictive factors for live birth outcome in women undergoing assisted conception and discover the modulating effect of age.PubMed, Embase, Medline, and Web of Science were searched for studies published until June 2021. We included studies that measured serum AMH levels and reported the subsequent live birth outcomes. Random effects models and hierarchical summary receiver operating characteristics (HSROC) models were used. The QUADAS-2 checklist was employed to assess the quality of the included studies.We included 27 studies (27,029 women) investigating the relationship between AMH and live birth outcome after assisted conception. The diagnostic odds ratios (DOR) from random effects models were ruled out due to high heterogeneity. Our findings suggested that AMH was associated with live birth. The DOR was 2.21 (95% CI 1.89-2.59), and 2.49 (95% CI 1.26-4.91) for studies on women with unspecified ovarian reserve and women with low ovarian reserve, respectively. The DOR of those with advanced ages was 2.50 (95% CI 1.87-2.60). For younger women, the DOR was 1.41 (95% CI 0.99-2.02). HSROCs showed that AMH had no predictive ability towards live birth in women with diminished ovarian reserve or younger age. Exclusion of Chinese cohorts lowered the heterogeneity.This study revealed that AMH had better prediction for live birth in advanced-age women. AMH may have implicative predictive value for assisted conception counseling of couples of advanced ages.

Mitochondrial biology and behavior are central to the physiology of liver. Multiple mitochondrial quality control mechanisms remodel mitochondrial homeostasis under physiological and pathological conditions. Mitochondrial dysfunction and damage induced by overnutrition lead to oxidative stress, inflammation, liver cell death, and collagen production, which advance hepatic steatosis to nonalcoholic steatohepatitis (NASH). Accumulating evidence suggests that specific interventions that target mitochondrial homeostasis, including energy metabolism, antioxidant effects, and mitochondrial quality control, have emerged as promising strategies for NASH treatment. However, clinical translation of these findings is challenging due to the complex and unclear mechanisms of mitochondrial homeostasis in the pathophysiology of NASH.

International audience; Deep oceans receive mercury (Hg) from upper oceans, sediment diagenesis, and submarine volcanism; meanwhile, sinking particles shuttle Hg to marine sediments. Recent studies showed that Hg in the trench fauna mostly originated from monomethylmercury (MMHg) of the upper marine photosynthetic food webs. Yet, Hg sources in the deep-sea chemosynthetic food webs are still uncertain. Here, we report Hg concentrations and stable isotopic compositions of indigenous biota living at hydrothermal fields of the Indian Ocean Ridge and a cold seep of the South China Sea along with hydrothermal sulfide deposits. We find that Hg is highly enriched in hydrothermal sulfides, which correlated with varying Hg concentrations in inhabited biota. Both the hydrothermal and cold seep biota have small fractions (

Congenital anomalies of the kidney and urinary tracts (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT.Clinical and genetic data were derived from a multicenter network (Chinese Children Genetic Kidney Disease Database, CCGKDD) and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children wereobtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan-Meier method and Cox proportional hazards models.A genetic diagnosis was established in 96 out of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs), and 4 (0.4%)with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 (95% confidence interval, 12.4-13.6) years, and twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors.The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.

IntroductionTo investigate whether rescue in vitro maturation (R-IVM) improves the reproductive outcomes among women undergoing intracytoplasmic sperm injection (ICSI) after one oocyte retrieved cycle.MethodsBetween January 2019 and December 2020, 2602 women who underwent ICSI in the Reproductive Medicine Center of Tongji Hospital, Wuhan, China, were included in our retrospective cohort study. There were 2112 women undergoing only ICSI and 490 women with R-IVM followed by ICSI. The intermediate reproductive outcomes and pregnancy outcomes were assessed, including the number of normally fertilized embryos, number of cleaved embryos, number of good-quality embryos, number of day-3 available embryos, number of embryos cultured past day-3, number of blastocysts, number of available blastocysts, biochemical pregnancy, miscarriage, clinical pregnancy and live birth. The perinatal outcomes were also assessed, including preterm birth and birth weight. The abovementioned outcomes were also calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group.Result(s)Compared with the women who underwent only ICSI, those who underwent ICSI with R-IVM had higher numbers of MII oocytes, normally fertilized embryos, cleaved embryos, day-3 available embryos, embryos cultured past day-3, and higher oocyte maturation rate, available embryo rate than women undergoing only ICSI. Additionally, we found that women undergoing ICSI with R-IVM had an increased chance of clinical pregnancy (adjusted OR=1.50, 95% CI: 1.17–1.93) and cumulative live birth (adjusted OR=1.35, 95% CI: 1.07–1.71). After propensity score matching (PSM), the cumulative live birth rate was 60.1% for women undergoing ICSI with R-IVM versus 54.9% for women undergoing only ICSI (OR=1.24, 95% CI: 0.94–1.63). The reproductive outcomes were also significantly different when calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group. All live births from R-IVM embryos were healthy and without malformations or complications.ConclusionR-IVM may improve the reproductive outcomes of women undergoing ICSI. It may also provide a reference for the safety of R-IVM. This study maybe support a routine application of R-IVM among patients who intend to undergo ICSI.

Polyethylene terephthalate (PET) are widely used in our daily life while they may be broken to smaller fractions as nano-sized PET (nPET) in the environment. The toxicity of nPET is still less studied. This work first evaluated the LD50 of different size of nPET (200 nm, S-nPET; 700 nm, B-nPET) in mice, then studied the health effects of single exposure to S/B-nPET at 200 mg/kg bw for 30 days. It was found that the LD50 was 266 mg/kg bw for S-nPET and 523 mg/kg bw for B-nPET, respectively, showing a size-dependent effect. S-nPET caused weight loss, cyst, intestinal obstruction, organ damage and mortality (40%), and perturbed gut microbiome and metabolome especially lipid metabolism, such as upregulated cholesterol, glycocholic, propionic acid, niacinamide, ectoine and xanthine, and downregulated arachidonic acid, anserine, histamine, while B-nPET did not. Serological analysis found S-nPET brought more lipid metabolic immune and neurological damage than B-nPET, confirming the size-dependent effect. To the best of our knowledge, this is the first report on the systematic toxicity of nPET to mice. Further studies are warranted for life-long effects of nPET. The protocol applied in this work may also be used for the study of the health effects of other plastics.

The detection potential of the active neutrino magnetic moment ($\nu_{a}$MM) and the active sterile transition magnetic moment ($\nu_{s}$MM) of the solar neutrino CE$\nu$NS process in future Dark Matter direct detection experiments is studied and compared with the respective allowed range to explain the Xenon1T excess. We find that the sensitivity to the $\nu_{a}$MM approaches to the level between $10^{-10}\mu_B$ and $10^{-11}\mu_B$, which is dominantly limited by the detection threshold. On the other hand, the future solar neutrino CE$\nu$NS detection would be powerful in probing the $\nu_{s}$MM for the sterile neutrino mass below 10 MeV, which could unambiguously test the $\nu_{s}$MM explanation of the Xenon1T excess. The sensitivity in the general framework with both $\nu_{a}$MM and $\nu_{s}$MM contributions is also derived., Comment: 22 pages, 5 figures

As typical transition metal dichalcogenides (TMDC), tungsten selenide (WSe2) nanosheets (nano-WSe2) are widely used in various fields due to their layered structures and highly tunable electronic and magnetic properties, which results in the unwanted release of tungsten (W) and selenium (Se) into the environment. However, the environmental effects of nano-WSe2 in plants are still unclear. Herein, we evaluated the impacts and fate of nano-WSe2 and micro-WSe2 in rice plants (Oryza sativa L.). It was found that both nano-WSe2 and micro-WSe2 did not affect the germination of rice seeds up to 5000 mg/L but nano-WSe2 affected the growth of rice seedlings with shortened root lengths. The uptake and transportation of WSe2 was found to be size-dependent. Moreover, W in WSe2 was oxidized to tungstate while Se was transformed to selenocysteine, selenomethionine, SeIV and SeVI in the roots of rice when exposed to nano-WSe2, suggesting the transformation of nano-WSe2 in rice plants. The exposure to nano-WSe2 brought lipid peroxidative damage to rice seedlings. However, Se in nano-WSe2 did not contribute to the synthesis of glutathione peroxidase (GSH-Px) since the latter did not change when exposed to nano-WSe2. This is the first report on the impacts and fate of nano-WSe2 in rice plants, which has raised environmental safety concerns about the wide application of TMDCs, such as WSe2 nanosheets.

As typical transition metal dichalcogenides (TMDC), tungsten selenide (WSe

Mercury (Hg) is harmful to the environment and human health. The gut plays important roles as the biological, chemical, mechanical, and immune barriers in animals and human beings. It has been known that Hg can be absorbed and methylated/demethylated in the gut, on the other hand, the impacts of Hg to the gut (especially the gut microbiota) is less studied. This review paper summarizes the impacts of inorganic Hg (IHg) and methyl Hg (MeHg) on gut barriers and the extraintestinal effects (damage to other organs such as the liver and brain). Both IHg and MeHg were found to cause intestinal microbial disorders, abnormal metabolites production, tight junction damage, and immune responses in the gut. The damage to the gut also contributed to the extraintestinal effects like the hepatotoxicity by IHg and the neurotoxicity by MeHg. In all, it is proposed that the gut should be considered as an important target tissue of Hg exposure, and the regulation of gut microbiota may have the potential for the prevention and control of the toxicity of Hg.

In many real applications, especially those involving data objects with complicated semantics, it is generally desirable to discover the relation between patterns in the input space and labels corresponding to different semantics in the output space. This task becomes feasible with MIML (Multi-Instance Multi-Label learning), a recently developed learning framework, where each data object is represented by multiple instances and is allowed to be associated with multiple labels simultaneously. In this paper, we propose KISAR, an MIML algorithm that is able to discover what instances trigger what labels. By considering the fact that highly relevant labels usually share some patterns, we develop a convex optimization formulation and provide an alternating optimization solution. Experiments show that KISAR is able to discover reasonable relations between input patterns and output labels, and achieves performances that are highly competitive with many state-of-the-art MIML algorithms.

Despite that iron-based catalysts are preferred for the high selectivity to value-added α-olefins via Fischer-Tropsch synthesis (FTS) reaction, the carbon deposition leads to deactivate catalyst more readily and CO2 selectivity as high as ~50% leads to low carbon efficiency. Herein, we developed an innovative approach to fabricate iron-based catalysts to deal with this issue. In detail, prepare Fe3O4 microsphere with an average particle size of ~580 nm via hydrothermal method and mix it with GO. The GO modification could effectively inhibit the sintering and coking of the large Fe3O4 microspheres (580 nm) by assisting its evolution into much smaller iron carbide nanocapsules (~9.1 nm). And the obtained catalyst exhibited excellent reaction activity, stability and high α-olefin selectivity. The addition of K into Fe3O4 microsphere produces major ɛ’-Fe2.2C about 58.9% in the evolution process and facilitates lower CO2 emission obviously.

Mercury (Hg) is a persistent and toxic metal while mercury selenide (HgSe) is generally considered as the environmental sink of Hg in its biogeochemical cycle. Recent studies found nano-sized HgSe (nano-HgSe) could be transformed by certain bacteria. This raises safety concerns about the application of selenium (Se) to curb Hg contamination in farmlands. Therefore, hydroponic experiments were performed in which rice plants were cultured with different concentrations of nano-HgSe and micro-sized HgSe (micro-HgSe) to explore their bioavailability and toxicity. It was found that both nano-HgSe and micro-HgSe did not affect the germination of rice seeds but affected the growth of rice seedlings. However, nano-HgSe could be more readily absorbed by roots and transferred to the aboveground parts compared to micro-HgSe. The highest Hg and Se levels were found to be 5255.67 ± 2496.14 μg/g and 1743.75 ± 61.87 μg/g, respectively in roots when exposed to 5000 mg/L nano-HgSe. Besides, small portion (1.2%) of methylmercury (MeHg) to total Hg was found accumulated in rice stem when exposed to 100 mg/L nano-HgSe, suggesting that nano-HgSe could be decomposed. Furthermore, nano-HgSe exposure brought oxidative damage to rice with decreased chlorophyll content and GSH-Px activity. In all, nano-HgSe was found to be more absorbable, transportable and methylated in rice plant compared to micro-HgSe. This suggests that although Se application in Hg contaminated farmland is an effective way to reduce the bioavailability of Hg, the risk of the possible remobilization of HgSe should not be neglected. Besides, the finding that nano-HgSe can act as an environmental source of Hg for plants deepens the understanding of biogeochemical cycle of Hg. More works are required to study the factors affecting the formation of nano-HgSe in the environment and the mechanisms of Hg methylation in rice plants after exposure to nano-HgSe.

To investigate whether rescue in vitro maturation (R-IVM) improves the reproductive outcomes among women undergoing intracytoplasmic sperm injection (ICSI) after one oocyte retrieved cycle.Between January 2019 and December 2020, 2602 women who underwent ICSI in the Reproductive Medicine Center of Tongji Hospital, Wuhan, China, were included in our retrospective cohort study. There were 2112 women undergoing only ICSI and 490 women with R-IVM followed by ICSI. The intermediate reproductive outcomes and pregnancy outcomes were assessed, including the number of normally fertilized embryos, number of cleaved embryos, number of good-quality embryos, number of day-3 available embryos, number of embryos cultured past day-3, number of blastocysts, number of available blastocysts, biochemical pregnancy, miscarriage, clinical pregnancy and live birth. The perinatal outcomes were also assessed, including preterm birth and birth weight. The abovementioned outcomes were also calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group.Compared with the women who underwent only ICSI, those who underwent ICSI with R-IVM had higher numbers of MII oocytes, normally fertilized embryos, cleaved embryos, day-3 available embryos, embryos cultured past day-3, and higher oocyte maturation rate, available embryo rate than women undergoing only ICSI. Additionally, we found that women undergoing ICSI with R-IVM had an increased chance of clinical pregnancy (adjusted OR=1.50, 95% CI: 1.17-1.93) and cumulative live birth (adjusted OR=1.35, 95% CI: 1.07-1.71). After propensity score matching (PSM), the cumulative live birth rate was 60.1% for women undergoing ICSI with R-IVM versus 54.9% for women undergoing only ICSI (OR=1.24, 95% CI: 0.94-1.63). The reproductive outcomes were also significantly different when calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group. All live births from R-IVM embryos were healthy and without malformations or complications.R-IVM may improve the reproductive outcomes of women undergoing ICSI. It may also provide a reference for the safety of R-IVM. This study maybe support a routine application of R-IVM among patients who intend to undergo ICSI.

Vulvar melanoma is a rare and aggressive tumor with a high risk of local recurrence and distant metastasis. The prognosis is poor with a 5-year overall survival rate of only 46.6%. Management of vulvar melanoma remains a clinical challenge. Recent evidences have shown that immune checkpoint inhibitors are effective in the treatment of vulvar melanoma.A 63-year-old woman with vulvar malignant melanoma suffered inguinal lymph node metastasis after vulvectomy and chemotherapy. She underwent inguinal lymph node dissection and inguinal radiotherapy. The tumor progressed again and she received immunotherapy.The tumor progressed again, and she was admitted to our hospital and received toripalimab combined with apatinib and abraxane.After 6 cycles of immunotherapy, the efficacy achieved partial remission. And with toripalimab as maintenance therapy, the patient achieved durable antitumor efficacy and good safety.In this rare case, the patient with metastatic vulvar malignant melanoma had durable antitumor efficacy and good safety when receiving toripalimab.

To compare the pharmacokinetic (PK) characteristics, investigate relative bioavailability, and provide data for potential additional bioequivalence trials between generic fidaxomicin (test (T) formulation) and the original brand (reference (R) formulation) in healthy Chinese subjects.An open, randomized, single-dose, cross-over study was conducted in 18 healthy Chinese subjects. The subjects randomly received T or R formulations and the alternative formulations were received after a 14-day wash-out period. Blood and fecal samples were collected and tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PK parameters were calculated using a non-compartmental model. Relative bioavailability considering commonly established bioequivalence criteria was assessed.CDespite the differences in exposure, PK characteristics and fecal recovery of the two formulations were similar, suggesting that an effective concentration of the generic fidaxomicin could be achieved locally in the gastrointestinal tract. Fidaxomicin was a highly viable drug, thus providing reference for future clinical study design.

Metal-organic frameworks (MOFs) have been a focus of research because of their unique porous structure, but they are usually not directly for electrocatalysis. Herein, we prepared a special class of Fe/Zn/Mo-based trimetallic hybrid zeolitic imidazolate frameworks by in situ solvothermal synthesis that have the potential to act directly as highly efficient oxygen evolution reaction electrocatalysts. This work provides a foundation for the preparation of multimetal MOFs and expands the investigation of electrocatalysts.

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung malignant tumor. Conventional chemotherapy has a suboptimal effectiveness. PSC has the characteristics of rapid disease progression and poor prognosis. We herein report a 56-year-old male patient with substantial smoking history was pathologically diagnosed as PSC, cT4N0M0 IIIA stage. Peripheral blood NGS showed TP53 mutation. The patient had poor tolerance to the first-line chemotherapy regimen “albumin paclitaxel + cisplatin,” but the severe anemia was significantly improved after 5 days of anti-angiogenic therapy with Anlotinib. At this time, the patient received anti-PD-1 immunotherapy with Tislelizumab. Half a month later, degree III liver injury occurred repeatedly. After excluding drug-induced liver injury, we found that HCV-RNA 3.10 × 105 IU/ml and suspended all anti-tumor therapy. After the start of anti-HCV treatment with Epclusa, the treatment of Tislelizumab combined with Anlotinib was restarted, and there was no liver injury after that. The patient received monthly maintenance therapy with Tislelizumab combined with Anlotinib to the present. The pulmonary lesions continued to decrease, and only one lung cavity is left. The patient has achieved clinical complete remission (CCR) with PSF over 20 months. Our findings suggest that Tislelizumab combined with Anlotinib may be a preferred strategy in PSC complicating TP53 mutation. Core tip: Immune-check point inhibitors (ICIs) have been reported for the treatment of PSC in a small number of case reports and retrospective analysis, but there are few reports of ICIs combined with anti-angiogenic drugs. This patient was diagnosed as locally advanced PSC complicated with TP53 mutation and hepatitis C. After 14 cycles of Tislelizumab combined with Anlotinib treatment (during the course of treatment, several courses were not treated on time for economic reasons, rather than adverse reactions), the patient has achieved CCR. III degree liver injury occurred during the treatment, and the liver function returned to normal range after anti-hepatitis C treatment, which did not affect the continued treatment of this regimen.

In this work, a new strategy is developed to design and synthesize quaternary catalysts NiS/CdS/MIL-101/PTCs (MIL = Materials of Institute Lavoisier, PTCs = polyoxo-titanium clusters) with excellent photocatalytic activity for H2 evolution. PTCs and NiS can be successfully integrated into CdS/MIL-101 system by multi-step solvothermal in situ reaction method. The as-synthesized photocatalysts integrated with NiS and PTCs exhibit the dramatically enhanced photocatalytic activity for hydrogen evolution, which is approximately 230 times higher than that of uncoupled catalyst CdS/MIL-101. It is more interesting that the photocatalytic activity can be tuned by structural evolution of PTCs. The photoelectrochemical characteristics of catalysts confirm that the drastic enhancement for photocatalytic H2-production activity was predominantly attributed to PTCs and NiS contributing to matching energy gap and improving visible-light response, respectively, and both inhibiting recombination of photogenerated electron-hole pairs. More importantly, this work can flourish the design idea derived from the relation of structure and application for photocatalysts.

The mechanical behavior of polyethylene (PE) co-polymerized with polyhedral oligomeric silsesquioxane (POSS) was studied by using molecular simulations. Simulation configurations consisted of aligned PE chains with POSS attached to the central chain and amorphous PE chains with different content POSS. From the simulations with aligned PE chains with POSS, it was found that the method for reinforcement was due to dislocation pile-up at POSS, and above a critical stress the dislocations traverse the POSS causing a sawtooth variation in the load-displacement curve. The stress-strain curves for amorphous PE-POSS bulk showed distinct elastic and plastic straining stages. Plastic straining consisted of hardening and slipping segments attributed to dislocation pile-up and chain sliding. Computational results were used to develop a reinforcement model to describe the mechanical response of PE-POSS bulk under uniaxial tension.

Background and Aims: Malignant biliary obstruction is always caused by tumors which are unresectable so that palliative stent placement is conducted for drainage of bile duct tree. Recently, irradiation stent with 125I seeds has been used to improve the stent patency and survival time of patients. We conducted this meta-analysis to evaluate the therapeutic efficacy and safety of biliary stent placement with 125I seeds compared with stent placement alone in patients with malignant biliary obstruction. Methods: We searched Pubmed, Web of Science, ClinicalTrials.gov, Cochrane Library, Embase and CNKI databases for all relevant studies up to 1 May 2020. Patient survival, stent patency, and adverse events were the primary outcome measured. Also, Review Manager 5.3 and Stata/SE15.0 were used to perform the analysis. Results: Eleven randomized controlled trials with a total of 767 patients were included for meta-analysis. Stent combined with 125I seeds showed lower risk of stent occlusion at 3 month (Odds Ratios(OR) = 0.15; 95%CI: 0.05-0.49, P =0.002), 6 month (OR = 0.18; 95%CI: 0.08-0.44, P = 0.0001), 9 month (OR = 0.10; 95%CI: 0.05-0.20, P < 0.00001) and 1 year (OR = 0.15; 95%CI: 0.07-0.31, P < 0.00001) and better mean survival (MD = 125days; 95% CI 91-159 days; P < 0.00001) compared with stent placement alone. Also, reconstructed Kaplan-Meier data demonstrated improved survival in patients treated with stent plus 125I seeds (hazard ratio(HR)= 1.886; 95% CI: 1.609 to 2.210; P < 0.0001) Moreover, our analysis did not show significant difference between the two groups about the risk of adverse events including abdominal pain, hemobilia, pancreatitis, cholangitis and cholecystitis. Conclusion: 125I seeds combined with stent demonstrated superior stent patency and improved survival time compared to stent alone with acceptable complications.

BACKGROUND The efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) is unknown. AIM To evaluate the efficacy of glucose-lowering drugs dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors in treating NAFLD and to perform a comparison between these treatments. METHODS Electronic databases were systematically searched. The inclusion criteria were: Randomized controlled trials comparing DPP-4 inhibitors, GLP-1 RAs, or SGLT2 inhibitors against placebo or other active glucose-lowering drugs in NAFLD patients, with outcomes of changes in liver enzyme [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] from baseline. RESULTS Nineteen studies were finally included in this meta-analysis. Compared with placebo or other active glucose-lowering drug treatment, treatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors all led to a significant decrease in ALT change and AST change from baseline. The difference between the DPP-4 inhibitor and SGLT2 inhibitor groups in ALT change was significant in favor of DPP-4 inhibitor treatment (P < 0.05). The trends of reduction in magnetic resonance imaging proton density fat fraction and visceral fat area changes were also observed in all the novel glucose-lowering agent treatment groups. CONCLUSION Treatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors resulted in improvements in serum ALT and AST levels and body fat composition, indicating a beneficial effect in improving liver injury and reducing liver fat in NAFLD patients.

Intercropping a Cd-accumulator with economically valuable crops is common in slightly or moderately Cd-polluted farmland soils. A field experiment was conducted to evaluate the effects of water-soluble chitosan (WSC) on the growth and Cd uptake of the Cd-accumulatorThis paper clearly focused on the accumulation and uptake of Cd in the system of intercropping of Cd-accumulator (

Model-independent reactor isotopic cross sections per fission are determined by global fits of the reactor antineutrino data from High-Enriched Uranium (HEU) reactor rates, Low-Enriched Uranium (LEU) reactor rates, and reactor fuel evolution data. Taking account of the implicit quasi-linear relationship between the fission fractions of $^{239}\rm{Pu}$ and $^{241}\rm{Pu}$ in the LEU reactor data, the Inverse-Beta-Decay (IBD) yields and their correlations of the fissionable isotopes $^{235}\rm{U}$, $^{238}\rm{U}$, and Pu's are obtained. The data-driven isotopic IBD yields provide an anomaly-free model for the reactor isotopic cross sections per fission, where better than 1\% accuracy of the expected reactor IBD yields can be achieved for future experiments., 11 pages, 4 figures. With more discussions and references added, accepted for publication at Physical Review D

Viral myocarditis (VMC) commonly triggers heart failure, for which no specific treatments are available. This study aims to explore the specific role of long non‐coding RNA (lncRNA) maternally expressed 3 (MEG3) in VMC. A VMC mouse model was induced by Coxsackievirus B3 (CVB3). Then, MEG3 and TNF receptor‐associated factor 6 (TRAF6) were silenced and microRNA‐223 (miR‐223) was over‐expressed in the VMC mice, followed by determination of ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). Dual‐luciferase reporter assay was introduced to test the interaction among MEG3, TRAF6 and miR‐223. Macrophages were isolated from cardiac tissues and bone marrow, and polarization of M1 or M2 macrophages was induced. Then, the expressions of components of NLRP3 inflammatory body (NLRP3, ASC, Caspase‐1), M1 markers (CD86, iNOS and TNF‐α) and M2 markers (CD206, Arginase‐1 and Fizz‐1) were measured following MEG3 silencing. In the VMC mouse model, MEG3 and TRAF6 levels were obviously increased, while miR‐223 expression was significantly reduced. Down‐regulation of MEG3 resulted in the inhibition of TRAF6 by promoting miR‐223. TRAF6 was negatively correlated with miR‐223, but positively correlated with MEG3 expression. Down‐regulations of MEG3 or TRAF6 or up‐regulation of miR‐223 was observed to increase mouse weight, survival rate, LVEF and LVFS, while inhibiting myocarditis and inflammation via the NF‐κB pathway inactivation in VMC mice. Down‐regulation of MEG3 decreased M1 macrophage polarization and elevated M2 macrophage polarization by up‐regulating miR‐223. Collectively, down‐regulation of MEG3 leads to the inhibition of inflammation and induces M2 macrophage polarization via miR‐223/TRAF6/NF‐κB axis, thus alleviating VMC.

Polychlorinated biphenyls (PCBs), as persistent organic pollutants, are environmental endocrine-disrupting chemicals (EDCs). We aim to investigate the effects of prepubertal exposure to PCBs on the reproductive development and expression and regulation of related genes in rats. Female rats were treated with Aroclor-1221 (A-1221) (4 mg/kg/day, 0.4 mg/kg/day) or castor oil daily from postnatal day (PND) 28 for 2 weeks by gavage. Morphological, histological, hormonal, and biochemical parameters were studied. Lower weight and relative weight of hypothalamus, earlier puberty onset, a longer length of the estrous cycle, lower serum estradiol and progesterone levels, accelerated ovarian folliculogenesis, and higher apoptotic index in the ovary were found. The in vitro fertilization study showed a lower fertilization rate and cleavage rate. The genetic study revealed higher expression of Kiss-1 mRNA and lower expression of GnRH mRNA in the hypothalamus and higher expression of AMH mRNA and lower expression of C-myc mRNA in the ovary. These confirmed the reproductive damage of A-1221 in rats.

Multi-label learning methods assign multiple labels to one object. In practice, in addition to differentiating relevant labels from irrelevant ones, it is often desired to rank relevant labels for an object, whereas the ranking of irrelevant labels is not important. Thus, we require an algorithm to do classification and ranking of relevant labels simultaneously. Such a requirement, however, cannot be met because most existing methods were designed to optimize existing criteria, yet there is no criterion which encodes the aforementioned requirement. In this paper, we present a new criterion, PRO Loss , concerning the prediction of all labels as well as the ranking of only relevant labels. We then propose ProSVM which optimizes PRO Loss efficiently using alternating direction method of multipliers. We further improve its efficiency with an upper approximation that reduces the number of constraints from $O(T^2)$ O ( T 2 ) to $O(T)$ O ( T ) , where $T$ T is the number of labels. We then notice that in real applications, it is difficult to get full supervised information for multi-label data. To make the proposed algorithm more robust to supervised information, we adapt ProSVM to deal with the multi-label learning with partial labels problem. Experiments show that our proposal is not only superior on PRO Loss , but also highly competitive on existing evaluation criteria.

Background Because the overall prognosis remains dismal for patients with resected pancreatic cancer (PC), we aimed to explore the prognostic impact of examined lymph node (ELN) count on lymph node (LN)-negative pancreatic body/tail ductal adenocarcinoma. Methods Patients' data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (National Cancer Institute, USA) to investigate the relationship between ELN count and survival outcomes of LN-negative pancreatic body/tail ductal adenocarcinoma. Results A total of 700 patients were included, and the median number of ELNs was 11. The respective 1-, 3-, 5-year overall survival (OS) rates were 75.3%, 37.7%, 30.3%, and the 1-, 3-, 5-year cancer-specific survival (CSS) were 78.3%, 41.7%, 34.5%. The X-tile analysis showed that 14 was the most optimal cutoff for both OS and CSS. Kaplan-Meier survival analysis indicated that patients with ELNs >14 had better OS and CSS than ELNs ≤14. Multivariate Cox analysis showed ELNs ≤14 was an independent risk factor for both OS [hazard ratio (HR), 1.357; 95% confidence interval (CI), 1.080-1.704; P=0.009] and CSS (HR, 1.394; 95% CI, 1.092-1.778; P=0.008). Conclusions ELN count is associated with the survival rate in patients with LN-negative pancreatic body/tail ductal adenocarcinoma. Accurate nodal staging for these patients requires more than 14 ELNs.

Recently, the system parameters of Cygnus X-1, i.e., the black hole mass M, the orbital inclination i and the source distance D, have been updated. As the input constraints of the continuum-fitting method, it is necessary to refine the spin with these new parameters. The Hard X-ray Modulation Telescope (HXMT, also named Insight) was successfully launched on June 15th, 2017 in China. In this work, we analyzed spectra obtained by the Insight-HXMT during 2017-2018 and re-estimated the spin via the continuum-fitting method. We first re-estimated the spin using old parameters and found the dimensionless spin parameter to be a ⁎ > 0.934 (3σ), which is consistent with previous measurements both from the continuum-fitting and iron-line fitting methods ( Gou et al. 2011 , Gou et al. 2014 ; Fabian et al. 2012 , Walton et al. 2016 , Tomsick et al. 2018 ). Then, when the new parameters were applied, we obtained an increased spin: a ⁎ > 0.967 (3σ), which is also consistent with the recent measurement (Zhao et al. 2020, submitted to ApJ) and also confirms an extreme Kerr black hole lying in this system.

Up to now, the experience that matching the total and local charge in advance will effect on the success of synthesis for metal–organic frameworks has been confirmed. In this work, we report two tetrazole-frameworks based on binuclear and trinuclear cluster Zn, respectively, namely [Zn2(btz)2(bdc)]·(solvents) (1) and [Zn3(atz)(bdc)3]·(cation)·(solvents) (2) (bdc = 1,4-benzenedicarboxylate acid, btz = 5-benzyl-1H-tetrazole, atz = 5-amino-1H-tetrazole). The result showed that pre-computing the charge can determine whether ionic template agent should present in the synthetic process, which could perfect the intentionality of design and synthesis of crystalline materials. Meanwhile compound 1 also exhibited the characteristic of reversible adsorption of iodine. Presented here is that pre-computing the total and local charge can determine whether ionic template agent should be added during the synthetic process, which could perfect the intentionality of design and synthesis of metal-organic frameworks.

Weak-label learning deals with the problem where each training example is associated with multiple ground-truth labels simultaneously but only partially provided. This circumstance is frequently encountered when the number of classes is very large or when there exists a large ambiguity between class labels, and significantly influences the performance of multi-label learning. In this paper, we propose LCForest, which is the first tree ensemble based deep learning method for weak-label learning. Rather than formulating the problem as a regularized framework, we employ the recently proposed cascade forest structure, which processes information layer-by-layer, and endow it with the ability of exploiting from weak-label data by a concise and highly efficient label complement structure. Specifically, in each layer, the label vector of each instance from testing-fold is modified with the predictions of random forests trained with the corresponding training-fold. Since the ground-truth label matrix is inaccessible, we can not estimate the performance via cross-validation directly. In order to control the growth of cascade forest, we adopt label frequency estimation and the complement flag mechanism. Experiments show that the proposed LCForest method compares favorably against the existing state-of-the-art multi-label and weak-label learning methods.

Weakly supervised learning aims at coping with scarce labeled data. Previous weakly supervised studies typically assume that there is only one kind of weak supervision in data. In many applications, however, raw data usually contains more than one kind of weak supervision at the same time. For example, in user experience enhancement from Didi, one of the largest online ride-sharing platforms, the ride comment data contains severe label noise (due to the subjective factors of passengers) and severe label distribution bias (due to the sampling bias). We call such a problem as ‘compound weakly supervised learning’. In this paper, we propose the CWSL method to address this problem based on Didi ride-sharing comment data. Specifically, an instance reweighting strategy is employed to cope with severe label noise in comment data, where the weights for harmful noisy instances are small. Robust criteria like AUC rather than accuracy and the validation performance are optimized for the correction of biased data label. Alternating optimization and stochastic gradient methods accelerate the optimization on large-scale data. Experiments on Didi ride-sharing comment data clearly validate the effectiveness. We hope this work may shed some light on applying weakly supervised learning to complex real situations.

In many real-world applications, the modeling environment is usually dynamic and evolutionary, especially in a data stream where emerging new class often happens. Great efforts have been devoted to learning with novel concepts recently, which are typically in a supervised setting with completely supervised initialization. However, the data collected in the stream are often in a semi-supervised manner actually, which means only a few of them are labeled while the great majority miss ground-truth labels. Besides, new classes hidden in unlabeled instances bring more challenges for the learning task. In this paper, we tackle these issues by a new approach called SEEN which consists of three major components: an effective novel class detector based on clustering random trees, a robust classifier for predictions on the known classes, and an efficient updating process that ensures the whole framework adapts to the changing environment automatically. The classifier produces known labels via label propagation that utilizes all labeled and part unlabeled data in the past which naturally describe the entire stream seen so far. Empirical studies on several datasets validate that the algorithm can accurately classify points on a dynamic stream with a small number of labeled examples and emerging new classes.

Objective The aim of this study was to assess the effectiveness of mindfulness meditation (MM) on anxiety, depression, stress and mindfulness in nursing students. Methods A comprehensive search and screening procedures were conducted to locate all MM interventions implemented with nursing students. For randomized controlled trials (RCTs) in accordance with the inclusion criteria, a search was conducted in PubMed, Embase, Web of Science, Medline, PsycINFO, Cumulative Index to Nursing and Allied Health (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), China Biology Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI) and Wanfang. Databases were retrieved from inception through August 2018. Additional studies were identified through hand searches and Internet searches. Two reviewers collected relevant data of eligible articles according to the data extraction tables. Based on Cochrane Handbook, critical appraisal of the methodological quality was assessed by two other reviewers. An Excel form was used to extract main characteristics of included RCTs. Meta-analysis and trial sequential analysis (TSA) were carried out using software RevMan 5.3 and TSA 0.9. Results Five RCTs with 257 nursing students were included. Only two studies were assessed as high quality and three studies were evaluated as moderate quality. Meta-analysis showed that, comparing with the control group, MM could significantly improve anxiety (SMD = −0.45, 95% CI −0.73 to −0.17, P = 0.001) and stress (SMD = −0.69, 95% CI −0.97 to −0.40, P < 0.001). TSA results confirmed that the outcome of the merger is credible. It could also significantly improve depression level of nursing students after 8 weeks intervention duration (SMD = −0.70, 95% CI −1.14 to −0.26, P = 0.002). However, there was no beneficial effect on depression level of nursing students with 1 week intervention duration (SMD = 0.09, 95% CI −0.42 to 0.59, P = 0.74) and its effects on mindfulness level of nursing students also did not show statistical significance (SMD = 0.37, 95% CI −0.04 to 0.77, P = 0.07). No definitive conclusions were drawn from the TSA. Conclusions The results of this meta-analysis indicated that MM could effectively reduce the level of anxiety and stress of nursing students. TSA confirmed that the results of meta-analysis are credible. For depression, it could also significantly improve depression of nursing students with 8 weeks intervention, but there was no significant effect on nursing students with 1 week intervention duration. There was also no beneficial effect on mindfulness level of nursing students. However, TSA indicated that the accumulated evidence is still inconclusive. We suggest that more well-designed clinical trials with large sample and higher quality would be required in future to draw a definitive conclusion.

This paper presents an extremely rare case of testicular metastasis arising from renal pelvis carcinoma. The testicle is a rare site of clinically detectable tumor metastasis, originating rarely from upper tract urothelial carcinoma (UTUC). There are only two cases concerning UTUC metastasis to the testis available in the literature. In this report, we presented a patient who developed serial testicle, lung, liver and retroperitoneal lymph node metastasis from primary urothelial carcinoma of the renal pelvis within one year after surgery and chemotherapy. In conclusion, for patients with a history of UTUC who present with testicular symptoms, clinicians should be highly alert for the possibility of malignant involvement at this site.

BackgroundWe aimed to develop and validate a new nomogram for predicting the risk of intracranial hemorrhage (ICH) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT).MethodsA retrospective study enrolled 553 patients with AIS treated with IVT. The patients were randomly divided into two cohorts: the training set (70%, n = 387) and the testing set (30%, n = 166). The factors in the predictive nomogram were filtered using multivariable logistic regression analysis. The performance of the nomogram was assessed based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA).ResultsAfter multivariable logistic regression analysis, certain factors, such as smoking, National Institutes of Health of Stroke Scale (NIHSS) score, blood urea nitrogen-to-creatinine ratio (BUN/Cr), and neutrophil-to-lymphocyte ratio (NLR), were found to be independent predictors of ICH and were used to construct a nomogram. The AUC-ROC values of the nomogram were 0.887 (95% CI: 0.842–0.933) and 0.776 (95% CI: 0.681–0.872) in the training and testing sets, respectively. The AUC-ROC of the nomogram was higher than that of the Multicenter Stroke Survey (MSS), Glucose, Race, Age, Sex, Systolic blood Pressure, and Severity of stroke (GRASPS), and stroke prognostication using age and NIH Stroke Scale-100 positive index (SPAN-100) scores for predicting ICH in both the training and testing sets (p < 0.05). The calibration plot demonstrated good agreement in both the training and testing sets. DCA indicated that the nomogram was clinically useful.ConclusionsThe new nomogram, which included smoking, NIHSS, BUN/Cr, and NLR as variables, had the potential for predicting the risk of ICH in patients with AIS after IVT.

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR

The MHC-peptide interaction has a subtle influence on host resistance to virus. This paper aims to study the relationship between MHC-peptide interaction and MHC-related virus-resistance.By 3D homology modeling, the structure of chicken BF2 molecule BF2*0201 (PDB code: 4d0d) was studied and compared with the known structures of BF2 molecule BF2*0401 (PDB code: 4e0r) to elucidate the characteristics of BF2*0201-binding antigenic peptides.The results show that due to the amino acid difference between the two binding groove of 4e0r and 4d0d, the size of the binding groove of the two are 1130 ų and1380 ų respectively, indicating the amino acid species that 4e0r binding peptide has lower selectivity than 4d0d; and because of large side chain conformation of Arg (especially Arg111) of 4e0r replaced by small side chain Tyr111 of 4d0d, the volume of central part of the binding groove of 4d0d is obviously larger than that of 4e0r, indicating that the restrictive of binding antigenic peptides for 4d0d is narrower than that of 4e0r; and on account of the chargeability of the binding groove of the two are different, namely the binding groove chargeability of 4e0r (strong positive polarity) and 4d0d (weak negative polarity).There are generally more peptides presented by the BF2 of B2 haplotype than by that of B4 haplotype, leading to more resistance of B2 than that of B4 to virus.

The theoretical framework of the neutrino electron excitation at low energies including the screening effect in semiconductor detectors is developed for the first time, both in the Standard Model and in the presence of the neutrino magnetic moment. We explore the contribution of the screening effect of semiconductors to the neutrino electron excitation based on the linear response theory and calculate the corresponding numerical results. We show that excitation rates from the neutrino magnetic moment are dramatically enhanced {by} the screening effect and the sensitivity can be significantly improved to the level of $10^{-13}\,\mu_{\rm B}$, much better than the current {laboratory and astrophysical} limits., Comment: 7 pages, 2 figures