ObjectiveTo investigate the therapeutic efficacy， influencing factors， and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus （HCV） infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1， 2021 to May 31， 2024 were enrolled， among whom there were 86 patients with compensated liver cirrhosis （CLC group） and 167 patients with chronic hepatitis C （CHC group）. The patients were treated with coblopasvir hydrochloride capsules （60 mg）/sofosbuvir tablets （400 mg） with or without ribavirin tablets for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment （SVR12） and safety， and the secondary outcome measures were the changes in liver function， renal function， blood routine， and liver stiffness measurements （LSM） after 4 weeks of treatment， after 12 weeks of treatment， and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups， and the Friedman test was used for comparison between multiple groups， while the Bonferroni method was used for paired comparison within each group； the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years， and there were 151 male patients （59.7%）. Of all patients， 33.99% （86/253） had liver cirrhosis， 25.69% （65/253） had hypertension， 10.67% （27/253） had HIV infection， 8.70% （22/253） had diabetes， 3.95% （10/253） had liver cancer， 1.98% （5/253） had chronic hepatitis B， and 7.91% （20/253） were treatment-experienced patients. As for genotype distribution， 2.77% （7/253） had genotype 1， 12.65% （32/253） had genotype 2， 66.01% （167/253） had genotype 3， 16.60% （42/253） had genotype 6， and 1.98% （5/253） had unknown genotype. The patients had an overall SVR12 rate of 92.09%， with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.086， 95% confidence interval ［CI］： 1.007 — 1.170， P=0.032） and HCC （OR=9.178， 95%CI： 1.722 — 48.912， P=0.009） were independent influencing factors for sustained virologic response. Compared with baseline data， the CLC group had significant reductions in alanine aminotransferase （ALT） （χ²=107.103， P0.05）， aspartate aminotransferase （AST） （χ²=90.602， P0.05）， and LSM （χ²=42.235， P0.05） after 12 weeks of treatment， while the CHC group had significant reductions in total bilirubin （χ²=15.113， P0.05）， ALT （χ²=202.237， P0.05）， AST （χ²=161.193， P0.05）， and LSM （χ²=37.606， P0.05）. The incidence rate of serious adverse events was 1.58%， and none of the patients withdrew from drug therapy； the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%， among which fatigue （17.39%） and nausea （2.37%） were the most common adverse events， and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.

Objective:To explore the relationship between memory bias, mental imagery, attention bias and depression in college students.Methods:From May to July 2024, a questionnaire was randomly distributed among 72 undergraduate students.The Beck depression inventory and Beck anxiety inventory were used to evaluate the depression and anxiety levels of all participants.The eye tracker was used to record the eye movement data of participants when observing emotional facial images.After the eye movement experiment, the scenario-based event completion task and prospective imagery task were used to collect the memory bias and mental imagery scores of all participants.SPSS 23.0 software was used for Spearman correlation analysis, and PROCESS 3.5 macro program was used for mediating effect test.Results:The scores of college students' negative memory bias, negative mental imagery, negative attention bias and depression were 0.40±0.15, 25.86±9.39, 0.41±0.14, 11.00(5.00, 20.00), respectively.Negative memory bias in college students was significantly and positively correlated with negative mental imagery, negative attention bias and depression ( r=0.832, 0.627, 0.834, all P<0.01).Negative mental imagery in college students was significantly and positively correlated with negative attention bias and depression ( r=0.692, 0.969, both P<0.01).Negative attention bias in college students was significantly and positively correlated with depression ( r=0.693, P<0.01).Negative mental imagery and negative attention bias had significant single chain mediating effect between negative memory bias and depression in college students, accounting for 16.61%(0.146/0.879), 15.70%(0.138/0.879)and 4.89%(0.043/0.879)of the total effect, respectively. Conclusion:There is a significant positive correlation between negative memory bias, negative mental imagery, negative attention bias and depression.Negative mental imagery and negative attention bias not only partially mediate the relationship between negative memory bias and depression in college students, but also have a chain mediating effect.

Objective:To explore the relationship between memory bias, mental imagery, attention bias and depression in college students.Methods:From May to July 2024, a questionnaire was randomly distributed among 72 undergraduate students.The Beck depression inventory and Beck anxiety inventory were used to evaluate the depression and anxiety levels of all participants.The eye tracker was used to record the eye movement data of participants when observing emotional facial images.After the eye movement experiment, the scenario-based event completion task and prospective imagery task were used to collect the memory bias and mental imagery scores of all participants.SPSS 23.0 software was used for Spearman correlation analysis, and PROCESS 3.5 macro program was used for mediating effect test.Results:The scores of college students' negative memory bias, negative mental imagery, negative attention bias and depression were 0.40±0.15, 25.86±9.39, 0.41±0.14, 11.00(5.00, 20.00), respectively.Negative memory bias in college students was significantly and positively correlated with negative mental imagery, negative attention bias and depression ( r=0.832, 0.627, 0.834, all P<0.01).Negative mental imagery in college students was significantly and positively correlated with negative attention bias and depression ( r=0.692, 0.969, both P<0.01).Negative attention bias in college students was significantly and positively correlated with depression ( r=0.693, P<0.01).Negative mental imagery and negative attention bias had significant single chain mediating effect between negative memory bias and depression in college students, accounting for 16.61%(0.146/0.879), 15.70%(0.138/0.879)and 4.89%(0.043/0.879)of the total effect, respectively. Conclusion:There is a significant positive correlation between negative memory bias, negative mental imagery, negative attention bias and depression.Negative mental imagery and negative attention bias not only partially mediate the relationship between negative memory bias and depression in college students, but also have a chain mediating effect.

Isolated vertigo due to vascular mechanisms manifests as vertigo, dizziness or imbalance only. Due to the lack of focal neurological symptoms or signs, it is often misdiagnosed as peripheral vestibular disease, resulting in serious adverse consequences. This article reviews the lesion location, cerebrovascular basis, clinical evaluation, and imaging examination of isolated vertigo caused by vascular mechanisms.

Objective:To explore the characteristics of attentional bias to emotional faces of depressed college students with alexithymia.Methods:Using self-rating depression scale (SDS) and the twenty-item Toronto alexithymia scale(TAS-20), 25 low alexithymic-currently depressed undergraduates (LA-CD group), 33 low alexithymic-non depressed undergraduates(LA-ND group) and 23 high alexithymic-currently depressed undergraduates(HA-CD group) were selected from 885 valid questionnaires.Using eye tracking system, emotional face pictures were selected as stimulus materials, and the relative gaze time(attention bias score) of experimental participants was analyzed by statistical methods such as covariance analysis and adjustment analysis to explore the attentional bias of depressed college students with alexithymia.Results:(1) Under the low level of alexithymia, there was significant difference in attentional bias between college students in depression group (-0.23±0.18) and non-depressed group (0.06±0.11) ( F=55.876, P<0.01). (2) There were significant differences in relative attention bias among LA-CD group (-0.234±0.150), HA-CD group(-0.070±0.153) and LA-ND group (0.064±0.149) ( F(2, 78)=27.685, P<0.01). According to Bonferroni test, compared to the LA-CD group, the HA-CD group and LA-ND group showed less negative attentional bias.(3) The interaction between total SDS score and total TAS-20 score showed significant difference.Alexithymia played a regulatory role between total SDS score and attentional bias( β=0.333, t=3.345, P<0.01). Conclusion:Both the depressed college students with high alexithymia and the non-depressed college students with low alexithymia show less negative attentional bias.Alexithymia plays a regulatory role between depression and attentional bias.

Objective:To explore potential role and mechanism of N6-methyladenine(m6A)RNA methylation regulators in prognosis and tumor immune microenvironment of cervical cancer.Methods:Clinical and survival data as well as RNA sequencing data were acquired from TCGA and GEO database.Expressions and correlation among m6A RNA methylation regulators were analyzed by bioinformatics analysis and tissue validation experiments.LASSO Cox regression analysis was used to generate a prognostic risk sig-nature based on m6A regulators.Two m6A-modification patterns were identified based on m6A regulators and their abundance of im-mune cell inflitration were analyzed by ssGSEA.Results:Compared with normal tissues,RBM15,IGF2BP2,IGF2BP3,FMR1,YTHDF1,METTL3 and YTHDF2 expressions were significantly up-regulated in cervical cancer tissues,while ZC3H13,METTL4,YTHDC1,FTO and ALKBH3 expressions were significantly down-regulated.Five m6A regulators HNRNPC,LRPPRC,METTL3,ELAVL1 and FMR1 were selected to establish prognostic risk signature,whose expressions in cervical cancer were verified by HPA database and qRT-PCR with good predictive value,and could be used as independent poor prognostic factor(AUC=0.734).Based on expressions of 25 m6A regulators,two m6A modification patterns m6Acluster A and m6Acluster B were determined.There were differ-ences between two groups in biological functions,signal pathways and immune cells infiltration levels in tumor microenvironment.Conclusion:m6A RNA methylation regulators are closely related to prognosis and immune infiltration of cervical cancer,which provides guidance for immunotherapy strategy.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

Objective To determine the difference in blood microcirculation recovery between normal frostbite and high-altitude frostbite during the wound healing.Methods Twenty four male rats were randomly divided into control group (n=8), normal frostbite group (n=8), and high-altitude group (n=8). The normal frostbite group rats were frozen to produce mid-degree frostbite models by controlling the freezing time with liquid nitrogen penetration equipment. The high-altitude frostbite group rats were acclimated to a hypoxic and low-pressure environment for 1 week, and then the high-altitude frostbite models were constructed by the same way with liquid nitrogen penetration apparatus. On days 3, 7, 11, 15, 19, and 23 after modeling, the recovery situation of blood circulation of each group was observed with contrast ultrasonography by injecting SonoVue micro-bubble into rats' tail. Finally, the micro-bubble concentration (MC) was calculated to confirm the blood circulation recovery with software Image Pro. ResultsAt different time points, the wound area of the high-altitude frostbite group was bigger than that of the normal frostbite group, and the MC of control group was always about (27±0.2)×109/ml. On day 3, 7, 11, 15, 19, and 23, the MC was significantly lower in the high-altitude frostbite group than in the control group and normal frostbite group (P<0.05). The MC of normal frostbite group was significantly lower than that of the control group on day 3, 7, 11, 15 and 19 (P<0.05). In addition, no obvious difference in MC was found between normal group and control group on the 23th day (P<0.05).Conclusion The blood microcirculation recovery after high-altitude frostbite is significantly slower than the normal frostbite.

BACKGROUND:Tissue-engineered transplantation technique has become an ideal therapeutic regimen for degenerative disc diseases through reconstituting the biological functions of the degenerated intervertebral discs.
OBJECTIVE:To construct a novel tissue-engineered annular fibrosus scaffold.
METHODS:Konjac glucomannan, nano-hydroxyapatite and colagen were used to fabricate a new tissue-engineered annular fibrosus scaffold by wet spinning, chemical crosslinking, and freeze drying methods. Afterwards, X-ray diffraction and Fourier transform infrared spectrometer were used to analyze the scaffold qualitative components, physico-chemical property, biomechanical performance and cytocompatibility.
RESULTS AND CONCLUSION:The bionic scaffold had a three-dimensional porous structure, with the average pore size of (425.8±47.3) μm, the average porosity of (73.4±5.6)%, and the water absorption of (718.6±24.3)%. In addition, the compressive strength of the scaffold was similar with that of the natural annular fibrosus. More importantly, the scaffold had good biocompatibility without cytotoxicity. These results show that the tissue-engineered annular fibrosus scaffold constructed by konjac glucomannan, nano-hydroxyapatite and colagen has proper three-dimensional porous structure, biocompatibility, porosity, water absorption and biomechanical strength.

Objective To investigate protective activity against Aβ25-35-induced cytotoxicity in PC12 cells of different extracts and ursolic acid, which were isolated from pyrola decorata. Methods Aβ25-35-induced cytotoxicity in PC12 cells was established as the model in vitro. The cultured PC12 cells were divided into blank control group, DMSO control group, model control group, different extract groups of pyrola decorate and ursolic acid(UA) group. The different extract groups included ether extract (PE), acetidin extract (AE), n-butanol extract (BE), the water extract (WE), 50% ethanol extract (HEE). MTT assay was used to test the optimum concentration, and the number of viable cells in culture medium was measured by ELISA at 490 nm wavelength. Results The cell viabilities in different extracts groups(PE, AE, BE, WE, HEE) were respectively 89.3%, 77.2%, 79. 2%, 75. 1% ,74. 0% at the concentration of 5. 0 mg ? mL-1 . Moreover, ursolic acid showed the best neuroprotective activity (88.9%) at the concentration of 500 μg?L-1 . Compared with model control group, the survival rate of each group was remarkably increased, and the protective activities of PE and UA were more significant among them. Conclusion Different polar extracts of pyrola decorata and isolated ursolic acid have neuroprotective effects on Aβ25-35-induced cytotoxicity in PC12 cells in certain degrees.