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This retrospective study investigated superficial retinal vessel density (SRVLD) and foveal avascular zone (FAZ) area using optical coherence tomography angiography (OCTA) in children with myopic anisometropia. We included 84 eyes of 42 individuals with myopic anisometropia and no posterior segment abnormalities. All eyes underwent OCTA. Individual SRVLD and FAZ area were measured on OCTA. Using a paired t -test, we compared the interocular difference between the fellow eyes for all the measurements. SRVLD was significantly higher in the relatively more myopic eyes than in the fellow eyes in the whole population and in patients with an interocular difference of >1.5 D ( p = 003 and 0.01, respectively). In patients with an interocular difference of ≤1.5 D in spherical equivalent refraction, only the nasal sector showed higher SRVLD in the less myopic eyes. SRVLD in the whole image and parafoveal sector was significantly lower in the dominant eye (paired t -test, p = 003 and 0.03, respectively), while other locations showed no difference. The area, perimeter, and circularity index in FAZ parameters showed no difference. SRVLD showed no significant differences between the two types of eyes, with an interocular difference of ≤1.5 D but increased in the relatively more myopic eyes than in the fellow eyes in children with myopic anisometropia, with an interocular difference of >1.5 D. Increasing SRVLD may show a compensatory increase to maintain retinal function and thus maintain normal visual function in the relatively more myopic fellow eyes. As the study to use patients as self-control with OCTA analysis in both eyes, this study provides some reference value for further interpretation of the pathogenesis of anisometropia.

Hepatic sinusoidal obstruction syndrome (HSOS) via exposure to pyrrolizidine alkaloids (PAs) is with high mortality and there is no effective treatment in clinics. Bear bile powder (BBP) is a famous traditional animal drug for curing a variety of hepatobiliary diseases such as cholestasis, inflammation, and fibrosis. Here, we aim to evaluate the protective effect of BBP against HSOS induced by senecionine, a highly hepatotoxic PA compound. Our results showed that BBP treatment protected mice from senecionine-induced HSOS dose-dependently, which was evident by improved liver histology including reduced infiltration of inflammatory cells and collagen positive cells, alleviated intrahepatic hemorrhage and hepatic sinusoidal endothelial cells, as well as decreased conventional serum liver function indicators. In addition, BBP treatment lowered matrix metalloproteinase 9 and pyrrole-protein adducts, two well-known markers positively associated with the severity of PA-induced HSOS. Further investigation showed that BBP treatment prevents the development of liver fibrosis by decreasing transforming growth factor beta and downstream fibrotic molecules. BBP treatment also alleviated senecionine-induced liver inflammation and lowered the pro-inflammatory cytokines, in which tauroursodeoxycholic acid played an important role. What's more, BBP treatment also decreased the accumulation of hydrophobic bile acids, such as cholic acid, taurocholic acid, glycocholic acid, as well. We concluded that BBP attenuates senecionine-induced HSOS in mice by repairing the bile acids homeostasis, preventing liver fibrosis, and alleviating liver inflammation. Our present study helps to pave the way to therapeutic approaches of the treatment of PA-induced liver injury in clinics.

The study examined the influence of social support on depression, including the mediating role of psychological resilience and the moderating role of geography. Questionnaires were completed by 424 economically disadvantaged college students in two provinces, X, a coastal province, and Y, an inland province. The results indicated that (1) the social support of economically disadvantaged college students was positively correlated to psychological resilience (β = 0.62, t = 11.22, p < 0.001); (2) the psychological resilience of economically disadvantaged college students was negatively correlated with depression (β = −0.24, t = −10.3, p < 0.001); (3) the social support of economically disadvantaged college students was negatively correlated with depression (β = −0.08, t = −2.85, p < 0.001); (4) the psychological resilience of economically disadvantaged college students played a partial mediating role between social support and depression; and (5) geography played a moderating role in the effect of social support on depression.

Background Acute respiratory distress syndrome (ARDS) represents a clinical syndrome featuring refractory hypoxemia. Several reports have identified the role of the gut microbiota in affecting the immune activity and pathological characteristics of respiratory disorders via the gut-lung axis. However, the precise metabolic mechanism remains unknown. The present work focused on investigating the processes by which gut microbiota influence ARDS and identifying potential therapeutic targets of ARDS. Methods The feces and serum samples of 23 ARDS patients were collected, and a lung injury model was generated by transplanting microbiota from ARDS patients into healthy C57BL/6J mice. The changes in the gut microbiota and metabolic phenotypes of the feces samples from ARDS patients and lung-injured mice were analyzed using 16sRNA sequencing technology and metabolomics based on 1H nuclear magnetic resonance (NMR), respectively. The effect of gut microbiota on ARDS was also explored after giving an oral vancomycin treatment to lung-injury mice. Further, enzyme-linked immunosorbent assay (ELISA) was used to evaluate the hyperinflammatory response in mice and intestinal permeability in ARDS patients. Additionally, qRT-PCR and staining were performed to analyze colonic barrier function and permeability. Results Firmicutes formed the vital species of microbiota that was different in lung-injury mice. Moreover, butyrate (produced by Firmicutes) was the most crucial metabolite in the feces samples of ARDS patients and lung-injury mice. Elisa and HE results showed aggravated functional disturbances in the intestinal barrier of ARDS patients and lung inflammation in the lung-injured mice. These phenomena were significantly alleviated after the oral administration of vancomycin. Besides, the utilization of butyrate in the colon of mice was increased considerably. The level of butyrate was reduced in the feces but increased in the colon. Conclusions Thus, vancomycin affects butyrate metabolism in the colon by influencing the gut microbiota. Modulating colonic butyrate metabolism could help treat ARDS.

The long-chain fatty acyl CoA synthetase (ACSLs) family of enzymes contributes significantly to lipid metabolism and produces acyl-coenzyme A by catalyzing fatty acid oxidation. The dysregulation of ACSL3 and ACSL4, which belong to the five isoforms of ACSLs, plays a key role in cancer initiation, development, metastasis, and tumor immunity and may provide several possible therapeutic strategies. Moreover, ACSL3 and ACSL4 are crucial for ferroptosis, a non-apoptotic cell death triggered by the accumulation of membrane lipid peroxides due to iron overload. Here, we present a summary of the current knowledge on ACSL3 and ACSL4 and their functions in various cancers. Research on the molecular mechanisms involved in the regulation of ferroptosis is critical to developing targeted therapies for cancer.

This paper extends the work of Zhang et al. (2008) to investigate the daily commuting patterns allowing both late arrival in the morning and early departure in the evening in a linear city. Given the fixed parking locations of morning commuters, the Nash equilibrium principle is employed to formulate commuters’ departure time choice in the evening and the user equilibrium principle in terms of daily travel cost is adopted to formulate the departure time choice of morning commuters. A combined regime of linear location-dependent parking fee and time-varying road toll is then proposed to reduce the total social cost (TSC) for the linear city. All the possible equilibrium traffic flows are analytically derived. The analytical results show that (1) commuters, who arrive at work early in the morning, may not depart early in the evening, but their evening trip costs must be lower; (2) when the parking spaces become denser, the evening commute starts earlier and the morning commute starts later; (3) a linear location-dependent parking fee could either advance or postpone the earliest departure time in the morning; (4) three parking modes, distinguished by the order in which commuters park, occur successively as the parking fee rate increases; and (5) an appropriate parking fee can always improve the system efficiency, but no matter how the parking fee is changed, it is impossible to completely eliminate the efficiency loss in the morning. Furthermore, a parking reservation regime joint with time-varying road toll is designed to minimize the TSC for the linear city. Finally, a set of numerical examples are presented to demonstrate the model's properties and these proposed regimes’ performance.

Objective: To explore the audiological characteristics of infant auditory neuropathy (AN) patients with cochlear microphonic (CM) recorded but no otoacoustic emission (OAE) response and clinically reduce the rate of missed diagnosis of AN. Design: Retrospective clinical study of medical data from 2003 to 2020. Setting: Otolaryngology head and neck surgery clinical hearing center. Participants: Eighteen infant AN patients with CM present and distortion product otoacoustic emission (DPOAE) absent in both ears were OAE absent group. Forty-four infant AN patients with CM and DPOAE present in both ears were OAE present group. Main outcome measures: Audiological characteristics. Results: 1. The age of onset in OAE absent group was 0.9 (0.02) years old, which was less than 1.11 (1.63) years old in OAE present group (P=0.041). 2. The CM threshold of OAE absent group was 80 (10) dB nHL, which was significantly higher (P

BACKGROUND The global outbreak of human severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection represents an urgent need for readily available, accurate and rapid diagnostic tests. Nucleic acid testing of respiratory tract specimens for SARS-CoV-2 is the current gold standard for diagnosis of coronavirus disease 2019 (COVID-19). However, the diagnostic accuracy of reverse transcription polymerase chain reaction (RT-PCR) tests for detecting SARS-CoV-2 nucleic acid may be lower than optimal. The detection of SARS-CoV-2-specific antibodies should be used as a serological non-invasive tool for the diagnosis and management of SARS-CoV-2 infection. AIM To investigate the diagnostic value of SARS-CoV-2 IgM/IgG and nucleic acid detection in COVID-19. METHODS We retrospectively analyzed 652 suspected COVID-19 patients, and 206 non-COVID-19 patients in Wuhan Integrated TCM and Western Medicine Hospital. Data on SARS-CoV-2 nucleic acid tests and serum antibody tests were collected to investigate the diagnostic value of nucleic acid RT-PCR test kits and immunoglobulin (Ig)M/IgG antibody test kits. The χ2 test was used to compare differences between categorical variables. A 95% confidence interval (CI) was provided by the Wilson score method. All analyses were performed with IBM SPSS Statistics version 22.0 (IBM Corp., Armonk, NY, United States). RESULTS Of the 652 suspected COVID-19 patients, 237 (36.3%) had positive nucleic acid tests, 311 (47.7%) were positive for IgM, and 592 (90.8%) were positive for IgG. There was a significant difference in the positive detection rate between the IgM and IgG test groups (P < 0.001). Using the RT-PCR results as a reference, the specificity, sensitivity, and accuracy of IgM/IgG combined tests for SARS-CoV-2 infection were 98.5%, 95.8%, and 97.1%, respectively. Of the 415 suspected COVID-19 patients with negative nucleic acid test results, 366 had positive IgM/IgG tests with a positive detection rate of 88.2%. CONCLUSION Our data indicate that serological IgM/IgG antibody combined test had high sensitivity and specificity for the diagnosis of SARS-CoV-2 infection, and can be used in combination with RT-PCR for the diagnosis of SARS-CoV-2 infection.

Gynura japonica (also named Tusanqi in Chinese) is used as a folk herbal medicine for treating blood stasis or traumatic injury. However, hundreds of hepatic sinusoidal obstruction syndrome (HSOS) cases have been reported after consumption of preparations made from G. japonica because it contains large amounts of hepatotoxic pyrrolizidine alkaloids (PAs). To date, blood pyrrole-protein adducts (PPAs) are suggested as biomarkers for the diagnosis of PA-induced HSOS in clinics. However, the concentration of PPAs in the blood is greatly affected by several factors including the amount of PA exposure, herb intake period, and blood sampling time after the last exposure. In present study, the kinetic characters of PPAs in serum and liver as well as other potential target organs were studied systematically and comprehensively following multiple exposures of PAs in G. japonica extract (GJE). As results, PPAs content reached to a plateau both in serum and liver after the mice were treated with GJE for 2 weeks on daily basis. PPAs cleared significantly slower in liver (T1/2ke∼184.6 h, ∼7.7 days) than in serum (T1/2ke∼95.8 h, ∼4.0 days). Although more than 90 % PPAs were removed 2 weeks after the last dosing, PPAs still persisted in the liver until the end of the experiment, i.e. 8 weeks after the last dosing. The results would be of great help for understanding the importance of PPAs for PA-induced toxicity and its detoxification.

Objective: As one member of the histone deacetylase inhibitor (HDACi) family, Sodium butyrate (NaB) was found out that could be used as a differentiation inducer of much cancer cell. But its effects on tumor microenvironment cells are not well recognized. The goal of this research is to investigate the effect of NaB on B16 melanoma and analysis its relevant mechanism. Methods: We observed the effect of sodium butyrate on B16 melanoma in vivo and in vitro. MTT method was performed to detect cell apoptosis rate after treatment. Tumor associated macrophage infiltration condition was detected by flow cytometry. Western-blotting and immunohistochemical method were used to detect the expression of tumor associated macrophage cytokines. Results: A certain concentration of sodium butyrate could effectively inhibit B16 melanoma growth in vivo and in vitro. Compared with the control group (45.00 ± 3.43%), macrophage differentiation in the 1.0g / kg group (37.54 ± 2.34%), 2.0g / kg group (41.62 ± 3.10%) and 3.0g / kg group (29.28 ± 4.42%) group were all inhibited to varying degrees. The inhibitory effect was most significant in the 5.0 g / kg group (19.92 ± 4.80%), and the difference was statistically significant (P

Background Circulating fibrinogen to pre-albumin ratio (FPR) and albumin to fibrinogen ratio (AFR) are effective factors for predicting the prognosis of colorectal cancer (CRC). However, the role of these two ratios in diagnosing early-stage CRC and identifying the stage II CRC subgroup with high relapse risk remains unknown. This study aimed to assess the potential of FPR and AFR in differential diagnosis and risk stratification of early-stage CRC. Methods A discovery (694 and 512 patients with benign colorectal polyps and stage I–II CRC, respectively) and validation (201 benign colorectal polyps cases and 202 stage I–II CRC individuals) cohorts were enrolled in this study. Receiver operating characteristic curve (ROC), Kaplan–Meier curve, and time-dependent ROC were used to evaluate the diagnostic efficacy of AFR and FPR in the two cohorts and overall population, and the discriminating role of FPR in identifying clinical high-relapse risk patients in comparison with common clinical characteristics in stage II CRC patients. Results The area under the curve (AUC) of the preoperative circulating FPR was higher than that of AFR in the diagnosis of stage I–II CRC from colorectal adenomas and benign colorectal polyps in the discovery and validation cohorts and overall population. Carcinoembryonic antigen (CEA) combined with FPR could effectively discriminate early-stage CRC from colorectal adenomas or benign polyps. Preoperative FPR could effectively distinguish stage II subgroups with high and low relapse risk. It was superior to common clinical characteristics in identifying high-risk surgical patients who could benefit from adjuvant chemotherapy (CT) [time-dependent AUC: 0.637 vs. 0.511, p p 20 had the highest recurrence (31.16%) and death rates (21.88%), with similar highest recurrence (30.70%) and death (26.82%) rates found in non-CT-treated patients with FPR > 20. Stage II CRC patients with 20 ≥ FPR > 15 could significantly benefit from postoperative CT, as the recurrence (33.30%) and death (35.71%) rates within non-CT treated patients were approximately five times higher than those of the CT-treated cases (6.77% and 7.41% for the recurrence and death rates, respectively). No significant difference in recurrence rate was observed between L-FPR (≤ 15) patients with (10.00%) or without CT (9.76%), indicating that these patients might not require to receive adjuvant CT after curative resection. Conclusions Preoperative FPR combined with CEA is superior to common tumor biomarkers, FPR, or AFR in distinguishing early-stage CRC from benign colorectal polyps. Circulating FPR can be an effective biomarker for identifying high-risk patients and choosing suitable therapeutics for early-stage CRC.

This study was designed to predict the Q-markers of Citri Reticulatae Pericarpium volatile oil and conduct quantitative analysis by GC-MS. The common components of Citri Reticulatae Pericarpium volatile oil were detected by GC-MS. The network pharmacology approaches were utilized for constructing the component-target network and protein-protein interaction(PPI) network, followed by the GO and KEGG pathway enrichment analysis to clarify the pharmacological effects of common components. Molecular docking was conducted to observe the biological activities of common components, thus identifying the Q-markers of Citri Reticulatae Pericarpium volatile oil. The obtained Q-markers were subjected to quantitative analysis by GC-MS. The GC-MS analysis of 19 batches of Citri Reticulatae Pericarpium volatile oil revealed three common components, namely, D-limonene, γ-terpinene, and myrcene. The common components were analyzed based on network pharmacology, and the results showed that Citri Reticulatae Pericarpium volatile oil mainly acted on the core targets GABRA1, GABRA6, GABRA5, GABRA3, and GABRA2 through D-limonene and γ-terpinene, with five important pathways such as nicotine addiction and GABAergic synapse involved. The core targets were mainly distributed in olfactory region, cerebral cortex, cerebellum, basal ganglia, hippocampus, and amygdala to exert the pharmacological effects. As revealed by molecular docking, D-limonene and γ-terpinene exhibited good biological activities, so they were identified as the Q-markers of Citri Reticulatae Pericarpium volatile oil. The results of quantitative analysis showed that the volume fraction of D-limonene was within the range of 0.77-1.03 μL·mL~(-1), and that of γ-terpinene within the range of 0.04-0.13 μL·mL~(-1). The prediction of D-limonene and γ-terpinene as the Q-markers of Citri Reticulatae Pericarpium volatile oil has laid an experimental foundation for the establishment of the quality evaluation standard for Citri Reticulatae Pericarpium volatile oil.

Glutamine metabolism (GM) plays a critical role in hepatocellular carcinoma (HCC); however, a comprehensive methodology to quantify GM activity is still lacking. We developed a transcriptome-based GMScore to evaluate GM activity and investigated the association of GMScore with prognosis and therapeutic resistance. Two independent HCC cohorts with transcriptome data were selected from The Cancer Genome Atlas (TCGA, n = 365) and the International Cancer Genome Consortium (ICGC, n = 231). The expression of 41 GM-associated genes were used to construct and validate GMScore. Several genomic or transcriptomic biomarkers were also estimated. Tumor response to immune checkpoint inhibitors (ICIs) was predicted using the tumor immune dysfunction and exclusion algorithm. GMScore was closely correlated with patient characteristics, including stage, histology grade, alpha-fetoprotein level, and vascular invasion. High GMScore was an independent risk factor for overall survival (OS) in both cohorts (HR = 4.2 and 3.91, both p < 0.001), superior to clinical indices and other biomarkers. High GMScore presented transcriptome features to indicate cell growth advantages and genetic stability, which was associated with poor OS of patients who received transcatheter arterial chemoembolization (TACE). High GMScore was also related to high expression of immune checkpoint genes, increased infiltration of regulatory T cells, and decreased infiltration of M1 macrophages. More importantly, high GMScore indicated poor predicted responses to ICIs, which could be verified in an ICI-treated melanoma cohort. In conclusion, GMScore is a strong prognostic index that may be integrated into existing clinical algorithms. A high GMScore may indicate resistance to TACE and ICIs based on its transcriptome and immune features. Validations using other HCC cohorts, especially ICI-treated HCC cohorts, are necessary.

This study investigates the strengthening mechanism and carbide precipitation behavior of medium Mn steel with Nb-Mo microalloy after cyclic quenching and austenite reverse transformation treatment. The results show that the Nb/Mo element not only precipitates (Nb,Mo)C in the grains, hindering the movement of dislocations and increases the strength, but also segregates at the austenite/ferrite grain boundary, thus delaying the transformation from austenite to ferrite. In addition, a large amount of nano-scale cementite is retained after cyclic quenching and austenite reverse transformation, which has a positive effect on the proportion of retained austenite in medium Mn steel. Moreover, the carbides with small size and low Mn content are dissolved, and the decomposed C and Mn content are beneficial to the nucleation of austenite during the intercritical annealing process at a temperature of 690 °C.

Type 1 diabetes (T1D) causes cognitive decline and has been associated with brain metabolic disorders, but its potential molecular mechanisms remain unclear.The purpose of this study was to explore the molecular mechanisms underlying T1D-induced cognitive impairment using metabolomics and lipidomics.We developed an optimized integration approach of metabolomics and lipidomics for brain tissue based on UPLC-Q-TOF-MS and analyzed a comprehensive characterization of metabolite and lipid profiles in the hippocampus and frontal cortex of T1D male mice with cognitive decline (T1DCD) and age-matched control (CONT) mice.The results show that T1DCD mice had brain metabolic disorders in a region-specific manner relative to CONT mice, and the frontal cortex exhibited a higher lipid peroxidation than the hippocampus in T1DCD mice. Based on metabolic changes, we found that microglia was activated under diabetic condition and thereby promoted oxidative stress and neuroinflammation, leading to neuronal injury, and this event was more pronounced in the frontal cortex than the hippocampus.Our results suggest that brain region-specific shifts in oxidative stress and neuroinflammation may contribute to diabetic cognitive decline, and the frontal cortex could be the more vulnerable brain region than the hippocampus.

Among thermoelectric materials, tin telluride has been attracting significant interest for its nontoxic and eco-friendly nature. Meanwhile, band engineering and ultrathin film technologies have bee...

Objective: To study the effect and mechanism of icariin on the migration, proliferation and apoptosis of mouse melanoma B16 cells. Methods: Mouse melanoma B16 cells were treated with icariin at different concentrations (0, 10, 20, 50 μmol / L) for 24 hours. Cell proliferation, morphology, apoptosis and migration ability were detected, and the expression of PI3K/AKT/ mTOR pathway related proteins was detected by Western blot assay. Results: After treatment with icariin, the inhibition rate and apoptosis rate of mouse melanoma B16 cells increased significantly with the increase of administration concentration (P < 0.05). Hoechst 33258 staining showed that the cells in the blank control group (0 μmol/L) were uniformly stained and the color was lighter, while the cells in the experimental group containing icariin were thicker in color. The higher the concentration of the icariin, the more obvious the degree of chromatin aggregation. The scratch healing rate of B16 cells and the cell count on the bottom of Transwell membrane decreased significantly with the increase of icariin concentration (P < 0.05). The results of protein detection showed that with the increase of administration concentration, the expression of MMP-9, MMP-2 and mTOR decreased significantly, while the ratio of PI3K/ pPI3K and AKT/pAKT increased significantly, and there was significant difference between the groups (P < 0.05). Conclusions: Icariin can effectively inhibit the expression of PI3K/ AKT/mTOR pathway related proteins in mouse melanoma B16 cells, thus inducing apoptosis of tumor cells, inhibiting cell migration and finally exerting antitumor effect.

As an environment-friendly alternative to traditional PbTe, many attempts have recently been made to improve thermoelectric SnTe. Effective strategies are mainly focused on valence band convergence, nanostructuring, interstitial defects, and alloying solubility. In particular, alloying SnTe with CdTe/GeTe triggers an inherent decline of valence band offset effectively owing to a high solubility of ∼20% of CdTe. However, to what level an additional element doping in low-solubility SnTe-CdTe alloys can play a role in enhancing the thermoelectric performance still remains a mystery. Here, a new strategy is shown that unexpected Bi doping, by alloying with only ∼3% CdTe, induces a significant enhancement of the thermoelectric figure of merit ZT to be ∼240% (ZT up to ∼1.3) at 838 K, which is mainly determined by the dramatically reduced lattice thermal conductivity above 800 K deriving from the exotic Bi doping and Cu-interstitial defects. More interestingly, combining experimental and theoretical evidences, the Bi-doping-driven band convergence is also beneficial to the improvement of thermoelectric performance below 800 K. The present findings demonstrate the extraordinary role of Bi for advancing the thermoelectric performance in SnTe alloys.

Summary Lattice vibrations in crystalline materials generate phonons as heat carriers for heat conduction, and the phonon dispersion (energy versus momentum) is fundamentally determined by the mass of lattice vibrators (atoms) and the interaction force between atoms. A significant manipulation of lattice thermal conductivity through a change in atomic mass usually requires a large variation in chemical composition, which is not always valid thermodynamically or may risk the resultant detriment of other functionalities (e.g., carrier mobility). Here we show a strategy of alternatively manipulating the interaction force between atoms through lattice strains without changing the composition, for remarkably reducing the lattice thermal conductivity without reducing carrier mobility, in Na0.03Eu0.03Sn0.02Pb0.92Te with stable lattice dislocations. This successfully leads to an extraordinarily high thermoelectric figure of merit, with the help of valence band convergence. This work offers both insights and solutions on lattice strain engineering for reducing lattice thermal conductivity, thus advancing thermoelectrics.

Objective To analyze the clinical characteristics of patients with unilateral auditory neuropathy (UAN), and to provide guidance for future clinical diagnosis and research. Methods Patients who were clinically diagnosed with UAN from 2004 to 2019 were included. Clinical characteristics, audiological features, imaging findings, genetic test results and management effect were summarized and followed. Results A total of 44 patients [mean age, 4.35 ± 4.39 years; 22 (50.00%) males and 22 (50.00%) females] were enrolled for analyses. Among the 38 patients who were tested by pure-tone or behavioral audiometry, the degree of hearing loss of the affected ear was characterized as mild in 2 ears (5.26%), moderate in 5 (13.16%), severe in 9 (23.68%) and profound in 22 (57.89%). For the 44 contralateral ears, 33 (75.00%) showed normal hearing and 11 (25.00%) presented with sensorineural hearing loss. Auditory brainstem responses were absent or abnormal in all 44 affected ears, while otoacoustic emissions and/or cochlear microphonics were present. Among the 18 patients who underwent magnetic resonance imaging (MRI), 7 (38.89%) presented cochlear nerve deficiency (CND). Nineteen candidate variants were found in 12 patients among the 15 UAN patients who were conducted targeted gene capture and next generation sequencing. Thirty patients were followed up by telephone to investigate their management effect. Conclusions Our study demonstrates comprehensive audiological features of patients with UAN to improve the clinical understanding and diagnosis. Some patients with UAN could show ipsilateral CND and MRI is essential to evaluate if the nerve is deficient. No pathogenic variants that directly related to the pathogenesis of UAN have been found in this study currently.

Objective Cancer elicited inflammation is the main environmental cause leading to carcinogenesis and metastasis of non-small cell lung cancer (NSCLC). Roles of the inflammatory biomarker in predicting the clinical efficacy of tyrosine kinase inhibitor (TKI) and prognosis of naive patients with advanced NSCLC need to be determined, and the best inflammatory predicted biomarker remains unknown. Methods A total of 178 eligible advanced NSCLC patients (124 and 54 cases within discovery and validation cohorts, respectively) who received first-line EGFR-TKI between July of 2014 and October of 2020 were enrolled in the present study. We detected circulating immune cell counting, albumin (Alb), pre-albumin (pAlb), ALP, AST, LDH, GGT, HDL-c, and fibrinogen (Fib) concentrations, and calculated 22 inflammatory ratios and scores. Logistic regression and Cox proportional hazards models were used to assess the impact of these ratios and scores on objective response and disease control rate (ORR and DCR) as well as progression-free survival (PFS) in these patients. Results Twenty-five percentage and 24.07% of NSCLC patients were observed objective response to the treatment of first-line EGFR-TKI in discovery and validation cohort, respectively. Univariate and multivariate Cox regression showed that high PLR, NPS, SII, SIS, mSIS, GLR and FPR as well as low PNI were significantly associated with poor PFS in discovery cohort. However, only high SII and FPR were found to be associated with unsatisfactory outcome in validation cohort. Time-dependent areas under ROC of FPR were 0.702 (0.517–0.888) in discovery cohort, and 0.767 (0.613–0.921) in validation cohort, which were extremely higher than the other biomarkers. The patients with FPR-SII combined score 2 harbored worse prognosis compared to the combined score 0 in discovery (plog-rank = 0.003, adjusted HR = 2.888, 95%CI = 1.500–5.560) and validation cohort (plog-rank = 0.001, adjusted HR = 3.769, 95%CI = 1.676–8.478) as well as overall population (plog-rank Conclusions High-grade cancer elicited inflammation could attenuates response and outcome in tyrosine kinase inhibitor naive patients with advanced NSCLC. FPR-SII combined score was the best inflammatory biomarker to monitor and predict the progression of advanced NSCLC patients with treatment of TKI.

This paper established the identification technology of the main root origin of three-year-old spring Panax notoginseng aiming at providing theoretical basis for the protection and traceability of geographical indication products of P. notoginseng. Forty-four samples of three-year-old spring P. notoginseng from Guangxi Baise, Yunnan Wenshan, Yunnan new cultivating regions. The stable isotopic ratios of carbon, nitrogen, hydrogen and oxygen were determined by elemental analysis and stable isotope mass spectrometer. Combined with Duncan multiple comparative analysis, fisher discriminant analysis and sequential discriminant analysis, a origin discriminant model for the main root of three-year-old spring P. notoginseng was established for 3 production areas of P. notoginseng. The geographical climate and environment of three production areas of P. notoginseng are obviously different. From Guangxi Baise-Yunnan Wenshan-Yunnan new cultivating regions, the longitude, average annual temperature and annual precipitation gradually decrease, and the elevation and latitude are increasing. The results of multiple comparative analysis showed that there were significant or very signi-ficant differences in the δ~(13)C,δ~(15)N,δ~2H,δ~(18)O of the main roots of P. notoginseng in three regions. The results of fisher's discriminant analysis and sequential discriminant analysis showed that the correct discriminant rates of the main roots of P. notoginseng for three regions were 80.05%,76.47% and 90.91%, respectively, based on four stable isotope ratios, with an average of 84.09%. Using stable isotope fingerprint and chemometrics method, we can distinguish the origin of the main raw materials and products of P. notoginseng.

Yu-Cui Liao,1,* Hou-Qun Ying,2,* Ying Huang,3,* Yan-Ran Luo,3 Cui-Fen Xiong,3 Ruo-Wei Nie,3 Xiao-Juan Li,4 Xue-Xin Cheng1 1School of Public Health; Jiangxi Provincial Key Laboratory of Preventive Medicine, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Department of Nuclear Medicine, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 4Department of Clinical Laboratory, Kunming Children’s Hospital, Kunming, Yunnan, 650500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue-Xin ChengSchool of Public Health; Jiangxi Provincial Key Laboratory of Preventive Medicine Nanchang University, No. 1 Of Minde Road, Nanchang, People’s Republic of ChinaTel/Fax +86 0791-86297662Email cxxncu@163.comBackground: Cancer-related inflammation is the main cause of the progression of mucinous colorectal adenocarcinoma (MCA). Circulating fibrinogen-to-pre-albumin ratio (FPR) is associated with the clinical outcome in colorectal cancer (CRC). However, the prognostic role of FPR and which is the best inflammatory prognostic biomarker within MCA remain unknown.Methods: We enrolled 157 patients with stage I–III MCA in this study. Kaplan-Meier curve, Cox regression, and time-dependent receiver operation characteristic curve analysis were performed to assess the prognostic value and efficacy of the neutrophil-to-albumin ratio (NAR), neutrophil-to-pre-albumin ratio (NPAR), albumin-to-alkaline phosphatase ratio (AAPR), albumin-to-globulin ratio (AGR), albumin-to-fibrinogen ratio (AFR), and FPR in these patients.Results:: We found that NAR, NPAR, and FPR were significantly associated with unsatisfactory recurrence-free survival (RFS) in patients with stage I–III MCA, and the predicted efficacy of FPR was superior to that of the other two inflammatory biomarkers. Moreover, patients with a high combined TNM-CA199-FPR score had worse outcomes, with a high predicted efficacy of up to 0.779 (0.703– 0.856). Using FPR, the patient was monitored for the recurrence up to two months earlier than that achieved using the common imaging techniques (4 vs 6 median months) in stage I–III MCA patients undergoing radical resection.Conclusion: FPR is the preferred inflammatory biomarker and commonly used for predicting and monitoring recurrence in stage I–III MCA patients. The combined TNM-CA199-FPR score is an economical, simple, effective, and independent prognostic factor for localized disease.Keywords: mucinous colorectal carcinoma, fibrinogen-to-pre-albumin ratio, prognosis, inflammation

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder. MicroRNAs (miRNAs) have been identified to be involved in different physiological and pathological processes. In this study, the role of miRNA-29a in the potential mechanism underlying the function of the intestinal mucosal barrier in IBS-D was analyzed. Human intestinal mucosal epithelia from patients with IBS-D (diagnosed as meeting the Rome IV criteria) and healthy volunteers were collected. An IBS-D mouse model was established via induction with trinitro-benzene-sulfonic acid (TNBS), and the mice were injected with miRNA-29a inhibitor. Using transmission electron microscopy (TEM), the epithelial ultrastructure of the human intestinal mucosa was examined. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, the expression level of miRNA-29a was assessed. ELISA was used to analyze the activity of D-lactate (D-LA) and diamine oxidase (DAO). Through immunohistochemistry, RT-qPCR and western blotting, the expression of tight junction protein ZO-1 (ZO-1) and claudin-1 (CLDN1) was examined. In the human intestinal mucosal epithelia from patients with IBS-D, miRNA-29a was upregulated, ZO-1 and CLDN1 were downregulated, and the junctional complex (JC) was faint and discontinuous. In the IBS-D mouse model, treatment with miRNA-29a inhibitor downregulated D-LA and DAO activity, and increased the expression of ZO-1 and CLDN1 in the intestinal mucosal epithelium. In conclusion, the present study revealed that miRNA-29a is involved in the pathogenesis of IBS-D, probably by downregulating ZO-1 and CLDN1 expression, suggesting that miRNA-29a is likely to be an important regulator of intestinal barrier function and could be a possible therapeutic target for IBS-D.

BackgroundAuditory brainstem response (ABR) test is widely used in newborn hearing screening and hearing disease diagnosis. Identifying and marking are challenging and repetitive tasks because of complex rules of ABR characteristic waveform and interference of background noise.MethodsThis study proposes an automatic method to recognize ABR characteristic waveform. First, binarization is created to mark 1024 sampling points accordingly. The selected characteristic area of ABR data is 0-8ms. The marking area is enlarged to expand feature information and reduce marking error. Second, a bi-directional long short-term memory (BiLSTM) network structure is established to improve relevance of sampling points, and an ABR sampling point classifier is obtained by training. Finally, mark points are obtained through thresholding.ResultsSpecific structure, related parameters, recognition effect, and noise resistance of network were explored in 614 sets of ABR clinical data, and recognition accuracy of waves I, III, and V can reach 92.91%.DiscussionThus, the proposed method can reduce the repetitive work of doctors and meet accuracy effectively. Therefore, this method has clinical potential.

Anode materials play an important role in the performance of rechargeable batteries and have been attracting much research interest. In this work, we have investigated the electrochemical properties of two-dimensional (2D) Janus MSSe (M = Ti or V) for potential applications as anode materials in alkali metal ion batteries from density functional theory (DFT), following the recent successful synthesis of 2D Janus MoSSe. Our DFT calculations suggest that 2D Janus TiSSe and VSSe are stable in the 1T phase and 1H phase, respectively. It is found that alkali metal atoms X (X = Li, Na or K) can be stably adsorbed on the surfaces of Janus MSSe, and have low diffusion energy barriers. Additionally, small volume changes are observed in Janus MSSe after the adsorption of alkali metal atoms. It is predicted that the MSSe-2X systems have low open circuit voltages and high capacities. Our results suggest that 2D Janus TiSSe and VSSe are potential anode materials for alkali metal ion batteries.

Application of organic amendments is an effective approach for improving soil organic carbon and soil fertility. To investigate the effects of different organic amendments on soil organic carbon and its labile fraction content, a batch of incubation experiments was conducted on the fluvo-aquic soil in Dongting Lake region, Hunan Province. There were six treatments, including soil amended with rice straw, soil amended with Chinese milk vetch, soil amended with bio-organic fertilizer, soil amended with pig manure, and soil amended with rice straw-derived biochar, with unamended soil as control. Each treatment had the same amount of carbon input. After 180 days of incubation, application of organic amendments increased soil labile organic carbon content. Application of bio-organic fertilizer, pig manure and rice straw-derived biochar significantly increased soil organic carbon content by 26.1%, 9.7% and 30.7%, respectively. There was no significant change in soil organic carbon content in rice straw and Chinese milk vetch treatments which were more favourable to the accumulation of soil dissolved organic carbon and microbial biomass carbon. Pig manure was more favourable to the accumulation of soil dissolved organic carbon. Bio-organic fertili-zer could benefit the accumulation of soil microbial biomass carbon and readily oxidizable organic carbon. Rice straw-derived biochar could promote the accumulation of soil microbial biomass carbon and light fraction organic carbon. Compared with rice straw, soil carbon pool management index was increased by 31.8%, 111.6%, 62.2% and 50.7% in Chinese milk vetch, bio-organic fertilizer, pig manure and rice straw-derived biochar treatments, respectively. The performance of bio-organic fertilizer, pig manure, and rice straw biochar was better than rice straw and Chinese milk vetch from the perspective of soil carbon sequestration and soil carbon pool management index.有机物料还田是提升农田土壤有机碳、培肥土壤的重要措施。为探讨不同有机物料的还田效果,采用室外培养方法,研究了在等碳输入条件下,施用水稻秸秆、紫云英、生物有机肥、猪粪和水稻秸秆生物炭对洞庭湖双季稻区潮土有机碳和活性有机碳组分含量的影响。结果表明: 经过180 d的培养试验,与不施用有机物料相比,施用有机物料提高了土壤活性有机碳含量。生物有机肥、猪粪和水稻秸秆生物炭处理分别使土壤有机碳含量显著提升了26.1%、9.7%和30.7%,水稻秸秆和紫云英对土壤有机碳含量的提升效应在试验期间并不显著。水稻秸秆和紫云英还田更有利于土壤可溶性有机碳和微生物生物量碳的积累,猪粪更有利于土壤可溶性有机碳的积累,生物有机肥更有利于土壤微生物生物量碳和易氧化有机碳的积累,水稻秸秆生物炭则更有利于土壤微生物生物量碳和轻组有机碳的积累。与水稻秸秆还田相比,紫云英、生物有机肥、猪粪和水稻秸秆生物炭还田使土壤碳库管理指数分别提高了31.8%、111.6%、62.2%和50.7%。从土壤固碳和土壤碳库管理指数来看,生物有机肥、猪粪和水稻秸秆生物炭的还田效果优于水稻秸秆和紫云英还田。.