Objective : To explore the therapeutic effect of extracellular vesicles(EVs) of Aspergillus flavus(A. flavus) on A. flavus infection. Methods: The EVs of A. flavus were isolated using ultracentrifugation and detected/identified by nanoparticle tracking analysis(NTA). Quantitative real-time PCR(qRT-PCR) and enzyme-linked immunosorbent assay(ELISA) kits were used to assess the effect of A. flavus EVs on the polarization of bone marrowderived macrophages(BMDMs) and the expression levels of several cytokines,including tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-6(IL-6),and interleukin-10(IL-10). The Galleria mellonella(G.mellonella) infection model was constructed. Three concentration groups of A. flavus EVs(0. 2,2,and 20 μg/larvae) were set as the experimental groups,and PBS was used as the control group for the infection model.Meanwhile,three forms of negative control groups were established,including the PBS group,the pierced controlgroup, and the negative control group. The therapeutic effect of A. flavus EVs on A. flavus infection was evaluated by the survival rate of the G. mellonella infection models. Results: The particle size of A. flavus EVs ranged from 20 to550 nm. A. flavus EVs could polarize BMDMs into both M1 and M2 phenotypes and induce the production of cytokines,including TNF-α,IFN-γ,IL-6,and IL-10. The results of the G. mellonella infection model showed that A.flavus EVs could improve the survival rate of G. mellonella after A. flavus infection. Conclusion The EVs produced by A. flavus can promote the expression of both pro-inflammatory and anti-inflammatory cytokines in BMDMs,induce M1 polarization and M2 polarization of BMDMs,and increase the survival rate of G. mellonella after A. flavus infection.

Objective:To explore the alterations in gray matter morphology and contributing factors in patients with post-infectious olfactory dysfunction (PIOD) using voxel-based morphometry (VBM) and surface-based morphometry (SBM), thereby providing scientific insights into the neuropathological mechanisms underlying PIOD.Methods:A total of 46 PIOD patients (PIOD group) and 46 normosmic volunteers (control group) were recruited from the Smell and Taste Disorders Clinic of Beijing Anzhen Hospital, Capital Medical University, between January 2020 and December 2024. All participants underwent olfactory psychophysical tests (Sniffin′ Sticks) and olfactory event-related potential (oERP) examination. High-resolution T1-weighted 3D MRI structural images were obtained for both groups. VBM was employed to analyze inter-group differences in gray matter volume, while SBM was used to assess cortical thickness and folding index. Correlations between gray matter volume in significant difference brain regions and disease duration, Sniffin′ Sticks scores, oERP parameters were analyzed. A two-tailed P<0.05 was considered statistically significant. Results:No significant differences were observed in age, sex, education level, or Mini-Mental State Examination (MMSE) scores ( t=1.80, χ2=0.41, t=0.17, t=1.77, all P>0.05). Compared with controls, the PIOD group showed significantly lower Sniffin′ Sticks scores ( t=28.70, P<0.001), prolonged oERP latencies and reduced amplitudes (all P<0.001). VBM revealed significantly reduced gray matter volume in the right orbitofrontal cortex (OFC) in the PIOD group ( t=5.38, P<0.001). SBM demonstrated decreased cortical thickness in the right OFC ( t=5.27, P<0.001), with no significant differences in folding index. The gray matter volume in the right OFC was negatively correlated with disease duration ( r=-0.61, P<0.001), but no significant correlations were found with Sniffin′ Sticks scores or oERP parameters. Conclusion:Patients with PIOD show atrophy in the right OFC, which correlates with disease duration, suggesting that persistent olfactory dysfunction may be associated with neurodegenerative changes.

Cervical cancer(CC),a common malignant tumor afflicting women,poses serious threats to their health.Therefore,it is critical to develop a thorough understanding of the molecular mechanisms underlying the pathogenesis of CC,and to identify new therapeutic targets and methods for early diagnosis.The multi-omics research in tumors,involving proteomics,transcriptomics,genomics,microbiomics,and metabolomic,offers valuable insights.The multi-omics analysis of biological samples from patients with cervical intraepithelial neoplasia(CIN)and CC can help clarify the pathways involved in the pathogenesis and development of CC.Furthermore,multi-omics studies have identified a number of molecules associated with CC,including actin,lumican,family member with sequence similarity 83(FAM83A),cadherin EGF-LAG seven-pass G-type receptor 3(CELSR3),and 5,10-methylenetetrahydrofolate reductase(MTHFR),all of which show potential to be used as new biomarkers.These biomarkers will help make early diagnosis,improve the survival and prognosis of CC patients,and ultimately reduce CC incidence and mortality.This review synthesizes current advances in multi-omics research on cervical cancer.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Objective To investigate the relationship between serum trimethylamine oxide(TMAO),neurofilament light chain protein(NfL),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)expression levels and short-term prognosis in aneurysmal subarachnoid hemorrhage(aSAH)patients.Method A total of 125 aSAH patients(aSAH group)and 125 healthy volunteers in the same period(control group)who were admitted in heji hospital affiliated to Changzhi Medical College from March 2020 to June 2023 were selected.The serum expression levels of TMAO,NfL and PGC-1α were compared between control group and aSAH group.The aSAH patients were followed up for 6 months after discharge.Their prognosis were evaluated using Glasgow Outcome Scale(GOS)and they were further divided into good prognosis and poor prognosis groups according to the GOS results.The serum expression levels of TMAO,NfL and PGC-1α were compared between the two groups.The poor prognosis influencing factors were analyzed by multivariate Logistic regression analysis,the serum TMAO,NfL and PGC-1α value in predicting poor prognosis were analyzed by receiver operating characteristic(ROC)curve.Result The expression levels of serum TMAO and PGC-1 α in the aSAH group were(2.63±0.36)μmol/L and(0.51±0.13)ng/mL,respectively,which were lower than those in the control group(3.18±0.57)μmol/L and(0.81±0.16)ng/mL(P<0.05).The expression level of serum NfL was significantly higher in the aSAH group(64.48±14.35 pg/mL)than in the control group(28.36±8.82 pg/mL)(P<0.05).Compared with the good prognosis group whose serum levels of TMAO and PGC-1 α were(2.80±0.80)μmol/L and(0.58±0.16)ng/mL,respectively,the poor prognosis group had significantly lower serum TMAO[(2.29±0.63)μmol/L]and PGC-1 α[(0.36±0.12)ng/mL](P<0.05).In contrast,poor prognosis group had a significantly higher level of NfL(76.70±15.61)pg/mL compared to good prognosis group(58.52±10.52)pg/mL(P<0.05).The proportion of patients with hypertension,patients with diabetes,patients with large or giant aneurysms,patients with Hunt Hess grade Ⅲ-Ⅳ,patients with onset to hospital time>12 h,and the level of C-reactive protein(CRP)were higher in the poor prognosis group than in the good prognosis group(P<0.05).Hunt Hess grade Ⅲ-Ⅳ,elevated serum CRP and NfL were independent risk factors for poor prognosis in aSAH patients(P<0.05),while elevated TMAO and PGC-1 α were protective factors(P<0.05).The area under the curve(AUC)of serum TMAO,NfL,PGC-1 α,and their combined prediction of poor prognosis in aSAH patients were 0.726,0.830,0.862,and 0.956,respectively.The AUC of the combined detection was greater than that of each indicator detected separately.Conclusion Serum TMAO and PGC-1α are lowly expressed in aSAH patients,and serum NfL is highly expressed,which are related to the occurrence of short-term poor prognosis,the combined detection of the three indicators has a high predictive value for short-term poor prognosis in aSAH patients.

Objective:To explore the alterations in gray matter morphology and contributing factors in patients with post-infectious olfactory dysfunction (PIOD) using voxel-based morphometry (VBM) and surface-based morphometry (SBM), thereby providing scientific insights into the neuropathological mechanisms underlying PIOD.Methods:A total of 46 PIOD patients (PIOD group) and 46 normosmic volunteers (control group) were recruited from the Smell and Taste Disorders Clinic of Beijing Anzhen Hospital, Capital Medical University, between January 2020 and December 2024. All participants underwent olfactory psychophysical tests (Sniffin′ Sticks) and olfactory event-related potential (oERP) examination. High-resolution T1-weighted 3D MRI structural images were obtained for both groups. VBM was employed to analyze inter-group differences in gray matter volume, while SBM was used to assess cortical thickness and folding index. Correlations between gray matter volume in significant difference brain regions and disease duration, Sniffin′ Sticks scores, oERP parameters were analyzed. A two-tailed P<0.05 was considered statistically significant. Results:No significant differences were observed in age, sex, education level, or Mini-Mental State Examination (MMSE) scores ( t=1.80, χ2=0.41, t=0.17, t=1.77, all P>0.05). Compared with controls, the PIOD group showed significantly lower Sniffin′ Sticks scores ( t=28.70, P<0.001), prolonged oERP latencies and reduced amplitudes (all P<0.001). VBM revealed significantly reduced gray matter volume in the right orbitofrontal cortex (OFC) in the PIOD group ( t=5.38, P<0.001). SBM demonstrated decreased cortical thickness in the right OFC ( t=5.27, P<0.001), with no significant differences in folding index. The gray matter volume in the right OFC was negatively correlated with disease duration ( r=-0.61, P<0.001), but no significant correlations were found with Sniffin′ Sticks scores or oERP parameters. Conclusion:Patients with PIOD show atrophy in the right OFC, which correlates with disease duration, suggesting that persistent olfactory dysfunction may be associated with neurodegenerative changes.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Objective To investigate the relationship between serum trimethylamine oxide(TMAO),neurofilament light chain protein(NfL),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)expression levels and short-term prognosis in aneurysmal subarachnoid hemorrhage(aSAH)patients.Method A total of 125 aSAH patients(aSAH group)and 125 healthy volunteers in the same period(control group)who were admitted in heji hospital affiliated to Changzhi Medical College from March 2020 to June 2023 were selected.The serum expression levels of TMAO,NfL and PGC-1α were compared between control group and aSAH group.The aSAH patients were followed up for 6 months after discharge.Their prognosis were evaluated using Glasgow Outcome Scale(GOS)and they were further divided into good prognosis and poor prognosis groups according to the GOS results.The serum expression levels of TMAO,NfL and PGC-1α were compared between the two groups.The poor prognosis influencing factors were analyzed by multivariate Logistic regression analysis,the serum TMAO,NfL and PGC-1α value in predicting poor prognosis were analyzed by receiver operating characteristic(ROC)curve.Result The expression levels of serum TMAO and PGC-1 α in the aSAH group were(2.63±0.36)μmol/L and(0.51±0.13)ng/mL,respectively,which were lower than those in the control group(3.18±0.57)μmol/L and(0.81±0.16)ng/mL(P<0.05).The expression level of serum NfL was significantly higher in the aSAH group(64.48±14.35 pg/mL)than in the control group(28.36±8.82 pg/mL)(P<0.05).Compared with the good prognosis group whose serum levels of TMAO and PGC-1 α were(2.80±0.80)μmol/L and(0.58±0.16)ng/mL,respectively,the poor prognosis group had significantly lower serum TMAO[(2.29±0.63)μmol/L]and PGC-1 α[(0.36±0.12)ng/mL](P<0.05).In contrast,poor prognosis group had a significantly higher level of NfL(76.70±15.61)pg/mL compared to good prognosis group(58.52±10.52)pg/mL(P<0.05).The proportion of patients with hypertension,patients with diabetes,patients with large or giant aneurysms,patients with Hunt Hess grade Ⅲ-Ⅳ,patients with onset to hospital time>12 h,and the level of C-reactive protein(CRP)were higher in the poor prognosis group than in the good prognosis group(P<0.05).Hunt Hess grade Ⅲ-Ⅳ,elevated serum CRP and NfL were independent risk factors for poor prognosis in aSAH patients(P<0.05),while elevated TMAO and PGC-1 α were protective factors(P<0.05).The area under the curve(AUC)of serum TMAO,NfL,PGC-1 α,and their combined prediction of poor prognosis in aSAH patients were 0.726,0.830,0.862,and 0.956,respectively.The AUC of the combined detection was greater than that of each indicator detected separately.Conclusion Serum TMAO and PGC-1α are lowly expressed in aSAH patients,and serum NfL is highly expressed,which are related to the occurrence of short-term poor prognosis,the combined detection of the three indicators has a high predictive value for short-term poor prognosis in aSAH patients.

Objective:To analyze the influencing factors for efficacy of microvascular decompression (MVD) in primary trigeminal neuralgia (PTN).Methods:A retrospective study was performed. Clinical data of 178 patients with PTN underwent MVD at Department of Neurosurgery, Affiliated Hospital Affiliated to Nantong University from January 2018 to April 2022 were collected. Efficacy was evaluated according to Brisman's criteria. Differences of MVD efficacy in patients with different clinical characteristics or different neurovascular characteristics were compared. Multivariate Logistic regression was used to analyze the independent influencing factors for MVD efficacy.Results:All patients were followed up for about 2 years; at the last follow-up, 164 patients (92.13%) had good postoperative efficacy (130 were cured, 28 were obvious improved, and 6 were improved); 14 patients (7.87%) had poor postoperative efficacy (10 were ineffective and 4 were relapsed). No significant difference in surgical efficacy was noted among patients with different gender, age, left/right lateral pain, disease courses or pain degrees ( P>0.05). Patients with different contact degrees between the trigeminal nerve and blood vessels, different distances between the trigeminal nerve and blood vessels, and different curvature degrees of the posterior trigeminal nerve had significantly different surgical efficacy ( P<0.05). Multivariate Logistic regression indicated that contact degrees between the trigeminal nerve and blood vessels ( OR=0.233, 95% CI: 0.080-0.675, P=0.007), distances between the trigeminal nerve and blood vessels ( OR=6.991, 95% CI: 3.261-14.984, P=0.000), and curvature degrees of the posterior trigeminal nerve ( OR=0.351, 95% CI: 0.158-0.776, P<0.001) were independent influencing factors for postoperative outcomes. Conclusion:The postoperative efficacy is good in patients with slight contact between the trigeminal nerve and blood vessels, with distance between the trigeminal nerve and blood vessels greater than 1×time median width of the trigeminal nerve (WTN), or with hypotenuse height of the arced trigeminal nerve less than 1/2 WTN.

Objective:To investigate the role of neutrophil CD 11b (nCD 11b), soluble CD 14 subtype (sCD 14-St) and mitochondrial coupling factor-6 (CF-6) in the risk stratification of disease outcome in neonatal sepsis and its clinical significance. Methods:The clinical data of 121 septic neonates from July 2019 to March 2020 in Shanxi Children′s Hospital were retrospectively analyzed. According to the neonatal critical illness score (NCIS), the neonates were divided into non-critical group (NCIS>90 scores) with 35 cases, critical group (NCIS 70 to 90 scores) with 49 cases, very critical group (NCIS<70 scores) with 37 cases. There were 25 cases with poor prognosis (death), and 96 cases with good prognosis (survival). The C-reactive protein (CRP), procalcitonin (PCT), nCD 11b, sCD 14-St and CF-6 before treatment were detected. The correlation between nCD 11b, sCD 14-St, CF-6 and disease severity was analyzed by Spearman method; the value of nCD 11b, sCD 14-St and CF-6 in predicting poor disease outcome in sepsis neonates was analyzed by the receiver operating characteristic (ROC) curve. Results:The nCD 11b, sCD 14-St, CF-6, PCT and CRP in critical group and very critical group were significantly higher than those in non-critical group: (414.68 ± 93.29) and (532.74 ± 101.85) MFI vs. (325.45 ± 71.90) MFI, (892.40 ± 113.72) and (1 249.53 ± 95.41) ng/L vs. (784.66 ± 103.72) ng/L, (84.79 ± 28.35) and (121.66 ± 34.27) ng/L vs. (42.59 ± 13.51) ng/L, (19.24 ± 6.30) and (34.96 ± 11.95) μg/L vs. (8.89 ± 2.24) μg/L, (109.49 ± 36.77) and (247.13 ± 82.06) mg/L vs. (56.84 ± 17.25) mg/L; the indexes in very critical group were significantly higher than those in critical group, and there were statistical differences ( P<0.05). Spearman correlation analysis result showed that nCD 11b, sCD 14-St and CF-6 were positively correlated with disease severity in sepsis neonates ( r = 0.719, 0.813 and 0.823; P<0.01). The nCD 11b, sCD 14-St, CF-6, PCT and CRP in poor prognosis neonates were significantly higher than those in good prognosis neonates: (618.58 ± 146.92) MFI vs. (374.55 ± 120.03) MFI, (1 516.91 ± 194.38) ng/L vs. (828.13 ± 175.67) ng/L, (165.84 ± 25.63) ng/L vs. (62.51 ± 16.75) ng/L, (43.46 ± 10.14) μg/L vs. (20.19 ± 6.30) μg/L and (321.09 ± 94.56) mg/L vs. (88.24 ± 29.19) mg/L, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of nCD 11b, sCD 14-St and CF-6 for predicting poor disease outcome in sepsis neonates were 0.763, 0.796 and 0.838 (95% CI 0.678 to 0.836, 0.713 to 0.864 and 0.760 to 0.899), and the AUC of combination the 2 indexes was 0.921 (95% CI 0.858 to 0.962). Conclusions:The nCD 11b, sCD 14-St and CF-6 are associated with the disease severity and prognosis in sepsis neonates, and can be used as markers for risk stratification of disease outcome and assessment prognosis.