To explore the protective effect of Angelica sinensis polysaccharide(ASP)on leptospiro-sis induced by pathogenic Leptospira infection,the golden hamster model of leptospirosis was se-lected for the experiment.The Leptospira and Leptospira+ASP groups were intraperitoneally injected with Leptospira interrogans serovar Lai strain 56601(1 × 10 6 per hamster).After infec-tion,the Leptospira+ASP group was injected intraperitoneally with ASP(50 mg/kg)for three consecutive days,while the Leptospira group was injected intraperitoneally with normal saline for three days.The experiment employed methods such as daily observation of the clinical symptoms of golden hamsters,statistics of the survival status of each group of golden hamsters,pathological damage of liver,kidney,and lung,bacterial load in organs,and the expression of inflammatory cy-tokines(IL-1β and TNF-α).The results indicated that ASP could effectively alleviate the clinical symptoms of the infected hamsters,enhance the survival rate,ameliorate the pathological damage of the body,reduce the bacterial load in various organs,and mitigate tissue inflammation.This study demonstrated for the first time that ASP has a protective effect on leptospirosis,providing medication guidance for the clinical treatment of leptospirosis.

Objective:To explore the neurophysiological features of the prefrontal-limbic-striatal circuit in patients with early-stage bipolar disorder without manic or hypomanic episodes, and its role in identifying early-stage bipolar disorder.Methods:From 2009 to 2019, a total of 155 hospitalized patients with major depressive disorder (MDD) from Nanjing Brain Hospital were selected after at least 5 years of follow-up, 31 patients with depression transitioned to bipolar disorder(ctBD group) and 76 patients remained the diagnosis of MDD(MDD group) were recruited.Sixty-two healthy controls matched for age, gender, and education years were selected as control group(HC group). Resting-state magnetoencephalography (MEG) data in eyes-open state of all subjects were collected.Data were analyzed based on the fieldtrip toolkit on the MATLAB platform. The key brain area of the prefrontal-limbic-striatal circuit were selected. Inter-group statistical analysis were conducted on the spectral energy and power-correlated functional connectivity at the theta, alpha, beta, and gamma frequency bands in the brain area of interest. In addition, the prediction model was constructed to early recognize bipolar disorder.Results:(1)There were statistically significant differences in the spectral energy of theta and alpha frequency bands in the prefrontal-limbic-striatal circuit among the 3 groups (cluster- F=120.50, 112.39, both P<0.05). The spectral energy of theta and alpha frequency bands in interest brain regions of prefrontal-limbic-striatal circuit in MDD group was lower than that in HC group (cluster- t=89.52, P<0.05). The spectral energy of theta band in prefrontal-limbic-striatal circuit in ctBD group was lower than that in HC group(cluster- t=105.82, P<0.05), and the spectral energy of alpha band in inferior frontal gyrus, orbitofrontal gyrus and caudate nucleus was lower than that in HC group (cluster- t=75.78, P<0.05), while there was no significant difference between the MDD group and the ctBD group ( P>0.05).(2)After FDR correction, there were statistically significant differences in functional connectivity between the left orbitofrontal gyrus and the right ventral striatum among the three groups (0.26 (0.13, 0.34), 0.12 (0.09, 0.24), 0.27 (0.20, 0.37), H=13.51, P<0.05, FDR correction). The strength of functional connectivity between the left orbitofrontal gyrus and the right ventral striatum in the MDD group was weaker than that in the HC group and the ctBD group (all P<0.05).(3)Binary Logistic regression analysis showed that the functional connectivity of beta frequency band between the left orbitofrontal gyrus and the right ventral striatum ( B=1.50, OR=4.50, 95% CI=1.73-11.70), the functional connectivity between the right orbitofrontal gyrus and the right amygdala( B=0.98, OR=2.68, 95% CI=1.18-6.13), the total HAMD score ( B=0.80, OR=2.28, 95% CI=1.36-3.67), the body weight factor score ( B=-1.99, OR=0.14, 95% CI=0.04-0.45), the anxiety factor score ( B=-0.99, OR=0.37, 95% CI=0.19-0.71), and sleep factor score( B=-1.14, OR=0.32, 95% CI=0.16-0.65)were the influencing factors for depression transitioned to bipolar disorder. Conclusion:The decreased resting low-frequency energy in the prefrontal-limbic-striatal circuit may be the common neural basis for the onset of unipolar and bipolar depression, and enhanced functional connectivity may be a potential neural circuit mechanism for depression transitioned to bipolar disorder. Functional connectivity combined with clinical manifestations is helpful for early recognition of bipolar disorder.

Objective To investigate the factors that influence ocular surface biology and visual acuity in individuals with diabetic dry eye(DDE)and analyze how these factors contribute to changes in visual quality.Methods Based on the disease duration,fasting blood glucose(FBG),and glycated hemoglobin(HbA1c)levels of patients with type 2 diabe-tes mellitus(T2DM),the DDE patients were divided into different groups.Logistic regression analysis was used to identify influencing factors related to ocular surface biology and visual quality in each group of DDE patients.Tear film stability was evaluated based on the tear film rupture time(BUT),Schirmer I test(SIt),and ocular surface disease index(OSDI).Lip-iview? Surface interferometers were used to measure tear film lipid layer thickness(LLT),meibomian gland loss rate(MGP),meibomian gland opening number(MGYLS),and meibomian gland secretion score(MGYSS).Wavefront aber-rometry was used to measure corneal wavefront aberration values at 4 mm and 6 mm pupil diameters.Ocular response ana-lyzer(ORA)was adopted to analyze corneal hysteresis(CH)and corneal resistance factor(CRF).Moreover,ELISA ex-periment to evaluate the trend of changes in inflammatory factors in tears.Results Logistic regression analysis revealed that T2DM duration,smoking history,FBG,HbA1c,total cholesterol(TC),triglycerides(TG),OSDI score,LLT,BUT,SIt,MGP,MGYLS,MGYSS,total higher-order aberrations,spherical aberration,coma aberration,trefoil aberration,tumor necrosis factor-α,interleukin-6,matrix metalloproteinase-9,receptor for advanced glycation end products,and insu-lin were all influencing factors for the risk of DDE(all P＜0.05).As the T2DM course prolonged and FBG or HbA1 c levels rose,tear film-related indicators(LLT,BUT,and SIt)and meibomian gland-related indicators(MGYLS and MGYSS)inpa-tients gradually decreased,while OSDI scores and MGP gradually increased(all P＜0.05).As the T2DM course prolonged and FBG or HbA1c levels rose,the total higher-order aberrations,spherical aberration,coma aberration,and trefoil aber-ration in DDE patients under 4 mm and 6 mm pupil diameters gradually increased;Meanwhile,best corrected visual acuity,corneal hysteresis,and corneal resistance factor gradually decreased;The contents of tumor necrosis factor-α,interleukin-6,matrix metalloproteinase-9,receptor for advanced glycation end products,and insulin in tears all gradually increased,while mucin-5AC gradually decreased(all P＜0.05).Conclusion With the prolongation of T2DM duration and the in-crease of FBG or HbA1c,the ocular surface inflammatory response in DDE patients gradually worsens,corneal biological function decreases,and visual quality deteriorates.Timely systemic and local interventions are of great significance for im-proving dry eye symptoms and visual quality in DDE patients.

Objective:To explore the neurophysiological features of the prefrontal-limbic-striatal circuit in patients with early-stage bipolar disorder without manic or hypomanic episodes, and its role in identifying early-stage bipolar disorder.Methods:From 2009 to 2019, a total of 155 hospitalized patients with major depressive disorder (MDD) from Nanjing Brain Hospital were selected after at least 5 years of follow-up, 31 patients with depression transitioned to bipolar disorder(ctBD group) and 76 patients remained the diagnosis of MDD(MDD group) were recruited.Sixty-two healthy controls matched for age, gender, and education years were selected as control group(HC group). Resting-state magnetoencephalography (MEG) data in eyes-open state of all subjects were collected.Data were analyzed based on the fieldtrip toolkit on the MATLAB platform. The key brain area of the prefrontal-limbic-striatal circuit were selected. Inter-group statistical analysis were conducted on the spectral energy and power-correlated functional connectivity at the theta, alpha, beta, and gamma frequency bands in the brain area of interest. In addition, the prediction model was constructed to early recognize bipolar disorder.Results:(1)There were statistically significant differences in the spectral energy of theta and alpha frequency bands in the prefrontal-limbic-striatal circuit among the 3 groups (cluster- F=120.50, 112.39, both P<0.05). The spectral energy of theta and alpha frequency bands in interest brain regions of prefrontal-limbic-striatal circuit in MDD group was lower than that in HC group (cluster- t=89.52, P<0.05). The spectral energy of theta band in prefrontal-limbic-striatal circuit in ctBD group was lower than that in HC group(cluster- t=105.82, P<0.05), and the spectral energy of alpha band in inferior frontal gyrus, orbitofrontal gyrus and caudate nucleus was lower than that in HC group (cluster- t=75.78, P<0.05), while there was no significant difference between the MDD group and the ctBD group ( P>0.05).(2)After FDR correction, there were statistically significant differences in functional connectivity between the left orbitofrontal gyrus and the right ventral striatum among the three groups (0.26 (0.13, 0.34), 0.12 (0.09, 0.24), 0.27 (0.20, 0.37), H=13.51, P<0.05, FDR correction). The strength of functional connectivity between the left orbitofrontal gyrus and the right ventral striatum in the MDD group was weaker than that in the HC group and the ctBD group (all P<0.05).(3)Binary Logistic regression analysis showed that the functional connectivity of beta frequency band between the left orbitofrontal gyrus and the right ventral striatum ( B=1.50, OR=4.50, 95% CI=1.73-11.70), the functional connectivity between the right orbitofrontal gyrus and the right amygdala( B=0.98, OR=2.68, 95% CI=1.18-6.13), the total HAMD score ( B=0.80, OR=2.28, 95% CI=1.36-3.67), the body weight factor score ( B=-1.99, OR=0.14, 95% CI=0.04-0.45), the anxiety factor score ( B=-0.99, OR=0.37, 95% CI=0.19-0.71), and sleep factor score( B=-1.14, OR=0.32, 95% CI=0.16-0.65)were the influencing factors for depression transitioned to bipolar disorder. Conclusion:The decreased resting low-frequency energy in the prefrontal-limbic-striatal circuit may be the common neural basis for the onset of unipolar and bipolar depression, and enhanced functional connectivity may be a potential neural circuit mechanism for depression transitioned to bipolar disorder. Functional connectivity combined with clinical manifestations is helpful for early recognition of bipolar disorder.

Objective To compare the node strength in white matter networks between depressive disorder and bipolar depression patients,analyze structural connectivity impairments across brain regions,and assess their diagnostic utility.Methods This longitudinal study initially enrolled 91 patients with a baseline diagnosis of depressive episode.All subjects underwent diffusion tensor imaging at recruitment and white matter structural weighted networks were constructed using deterministic fiber tracking.After≥9 years of naturalistic follow-up,23 patients who maintained a diagnosis of major depressive disorder(MDD group)and 18 patients who maintained a diagnosis of bipolar disorder(BD group),while 30 demographically matched healthy controls(HC group)were included for comparison.The differences in nodal connection strength within the brain white matter networks among the three groups were compared.Furthermore,the receiver operator characteristic(ROC)curve was utilized to evaluate the diagnostic value of the differential brain regions in distinguishing between MDD and BD.Results In the left anterior cingulate gyrus,the node strength was lower in the BD than in the MDD group(3.89±0.76 vs.4.74±0.60).However,the node strength in the right caudate nucleus(4.94±1.26 vs.3.46±0.99)and right globus pallidus(1.98±0.67 vs.1.25±0.29)was higher in the BD than in the MDD group(P<0.01,FWE-corrected).The combined connectivity strengths of three brain regions—the left anterior cingulate gyrus,right caudate nucleus and right globus pallidus—were used to differentiate between MDD and BD,and an ROC curve was plotted,with an area under the curve(AUC)of 0.95(95%CI:0.91～0.99;P<0.001).The sensitivity and the specificity were 0.89 and 0.87,respectively.Conclusion The differences in node strength between patient groups may serve as a potential neuroimaging biomarker.Integration of node connectivity strengths from these differential brain regions can achieve superior discrimination accuracy.

Objective:To evaluate the efficacy and safety of dupilumab in the treatment of moderate-to-severe atopic dermatitis (AD) in infants aged 6 months to 2 years.Methods:A prospective cohort study was conducted. Children aged 6 months to 2 years with moderate-to-severe AD were enrolled from the Department of Dermatology, Children′s Hospital of Chongqing Medical University between July 2022 and March 2023. Children weighing 5 to < 15 kg received subcutaneous injections of dupilumab at a dose of 200 mg every 4 weeks, while those weighing 15 to < 30 kg received subcutaneous injections of dupilumab at a dose of 300 mg every 4 weeks. Three age-matched healthy children were recruited as controls at the same time. Clinical assessments were performed at weeks 0, 2, 4, 8, 12, and 16 by using the parameters scoring AD (SCORAD), eczema area and severity index (EASI), investigator′s global assessment (IGA), body surface area (BSA) involvement, patient-oriented eczema measure (POEM), pruritus numerical rating scale (NRS), sleep NRS, and infants′ dermatitis quality of life (IDQoL) index. The primary efficacy endpoint was the proportion of patients achieving an IGA score of 0 or 1 (IGA0/1) at week 16, and the key secondary efficacy endpoint was the proportion of patients achieving at least 75% improvement from baseline in EASI (EASI75) at week 16. In addition, serum immunoglobulin (Ig) E, IgG, IgM, and IgA levels and peripheral blood eosinophil counts were measured at weeks 0, 4, and 16. Peripheral blood T helper (Th) cell subsets were analyzed in 10 AD patients and 3 healthy children at baseline by flow cytometry, and 6 AD patients underwent repeat testing at week 16. Adverse reactions were recorded throughout treatment. Changes in clinical scores over time after dupilumab treatment were analyzed using repeated-measures analysis of variance, and changes in serum total IgE levels were analyzed using generalized estimating equations.Results:A total of 12 children with AD were enrolled, including 8 males and 4 females, aged 1.5 ± 0.3 years, and the baseline SCORAD was 64.8 ± 9.9 points. Compared with baseline, SCORAD, EASI, IGA, BSA, POEM, pruritus/sleep NRS, and IDQoL scores were all significantly reduced at week 2 (all P < 0.05), and continued to decrease at weeks 4, 8, 12, and 16. At week 16, the IGA scores decreased from 3.9 ± 0.3 points at baseline to 1.7 ± 0.9 points, with 9 patients achieving IGA0/1; the EASI scores decreased from 28.1 ± 12.4 points at baseline to 4.9 ± 5.4 points, with 9 patients achieving EASI75. Compared with baseline, serum total IgE levels were significantly reduced at weeks 4 and 16 (Wald χ2 = 11.51, P = 0.003). At baseline, the proportion of Th2 cells among total CD3 +CD4 + T cells in patients was significantly higher than that in healthy controls (6.3% ± 1.3% vs. 4.3% ± 0.8%, t = 2.45, P = 0.032) ; at week 16, the proportion of Th2 cells in patients (5.3% ± 2.0%) was significantly lower than that at baseline ( t = 5.56, P = 0.003). The proportion of Th1/17 cells increased from 2.2% ± 1.5% at baseline to 3.9% ± 2.1% at week 16 ( t = 3.51, P = 0.007), whereas the proportions of Th1 and Th17 cell subsets showed no statistical significance compared with baseline (both P > 0.05). One patient experienced an injection-site reaction and another developed fever, but no treatment-related serious adverse reactions were observed. Conclusions:Dupilumab demonstrated favorable efficacy and safety in infants aged 6 months to 2 years with moderate-to-severe AD. In addition, dupilumab could decrease the proportion of Th2 cell subsets and serum levels of total IgE.

Cervical cancer is one of the most common gynecological malignant tumors in China. Given their lack of obviously early symptoms, more than half of patients with cervical cancer are diagnosed in the middle and late stages of this malignancy, resulting in poor prognosis. Finding new therapeutic targets is the current research direction. Metabolomics, as a new omics technology, is expected to provide new targets for tumor precision diagnosis and treatment through the analysis of the changes and potential mechanisms of metabolites in tumor occurrence and development by chromatography, mass spectrometry, and other technologies. Herein, we review the research methods of metabolomics; metabolic characteristics of cervical cancer; and progress of the research on metabolomics in cervical cancer diagnosis, curative effect prediction, and prognosis evaluation to provide new ideas for the precise diagnosis and treatment of cervical cancer.

To explore the protective effect of Angelica sinensis polysaccharide(ASP)on leptospiro-sis induced by pathogenic Leptospira infection,the golden hamster model of leptospirosis was se-lected for the experiment.The Leptospira and Leptospira+ASP groups were intraperitoneally injected with Leptospira interrogans serovar Lai strain 56601(1 × 10 6 per hamster).After infec-tion,the Leptospira+ASP group was injected intraperitoneally with ASP(50 mg/kg)for three consecutive days,while the Leptospira group was injected intraperitoneally with normal saline for three days.The experiment employed methods such as daily observation of the clinical symptoms of golden hamsters,statistics of the survival status of each group of golden hamsters,pathological damage of liver,kidney,and lung,bacterial load in organs,and the expression of inflammatory cy-tokines(IL-1β and TNF-α).The results indicated that ASP could effectively alleviate the clinical symptoms of the infected hamsters,enhance the survival rate,ameliorate the pathological damage of the body,reduce the bacterial load in various organs,and mitigate tissue inflammation.This study demonstrated for the first time that ASP has a protective effect on leptospirosis,providing medication guidance for the clinical treatment of leptospirosis.

Objective To compare the node strength in white matter networks between depressive disorder and bipolar depression patients,analyze structural connectivity impairments across brain regions,and assess their diagnostic utility.Methods This longitudinal study initially enrolled 91 patients with a baseline diagnosis of depressive episode.All subjects underwent diffusion tensor imaging at recruitment and white matter structural weighted networks were constructed using deterministic fiber tracking.After≥9 years of naturalistic follow-up,23 patients who maintained a diagnosis of major depressive disorder(MDD group)and 18 patients who maintained a diagnosis of bipolar disorder(BD group),while 30 demographically matched healthy controls(HC group)were included for comparison.The differences in nodal connection strength within the brain white matter networks among the three groups were compared.Furthermore,the receiver operator characteristic(ROC)curve was utilized to evaluate the diagnostic value of the differential brain regions in distinguishing between MDD and BD.Results In the left anterior cingulate gyrus,the node strength was lower in the BD than in the MDD group(3.89±0.76 vs.4.74±0.60).However,the node strength in the right caudate nucleus(4.94±1.26 vs.3.46±0.99)and right globus pallidus(1.98±0.67 vs.1.25±0.29)was higher in the BD than in the MDD group(P<0.01,FWE-corrected).The combined connectivity strengths of three brain regions—the left anterior cingulate gyrus,right caudate nucleus and right globus pallidus—were used to differentiate between MDD and BD,and an ROC curve was plotted,with an area under the curve(AUC)of 0.95(95%CI:0.91～0.99;P<0.001).The sensitivity and the specificity were 0.89 and 0.87,respectively.Conclusion The differences in node strength between patient groups may serve as a potential neuroimaging biomarker.Integration of node connectivity strengths from these differential brain regions can achieve superior discrimination accuracy.

Objective: To evaluate the therapeutic potential and underlying mechanisms of action of propolis in db/db mice. Methods: The chemical composition of propolis was analyzed using UHPLC-MS/MS. Thirty mice, including six wt/wt and 24 db/db mice, were randomly assigned to four groups (n = 6 per group): control, model, metformin (250 mg/kg), low dose propolis (100 mg/kg), and high dose propolis (HDP; 400 mg/kg). Treatments were administered orally for four weeks. Body weight and FBG levels were recorded weekly, and an oral glucose tolerance test was conducted on the 25th day. Serum levels of FIN, GSP, connecting peptide, AST, ALT, HDL, LDL, TG, and TC were quantified using ELISA. Liver histopathology was assessed using H&E and PAS staining. Western blotting was performed to examine the expression levels of NF-κB, phosphorylated NF-κB, IκBα, pIκBα, and AKT in liver tissues. Results: The top 10 metabolites of propolis were identified in positive and negative ion modes. The HDP group exhibited a significant reduction in FBG levels, body weight, connecting peptide levels, homeostatic model assessment of β-cell function scores, and homeostasis model assessment of insulin resistance scores (all P < .05). GSP levels were significantly reduced in both treatment groups (all P < .001). The HDP group also exhibited a reduction in TC and LDL levels (both P < .05), whereas HDL levels increased in both treatment groups (all P < .05). Liver weight, AST levels, and ALT levels were reduced in both treatment groups (all P < .05). Histological analysis revealed improved liver morphology. Protein analysis demonstrated downregulation of phosphorylated NF-κB and phosphorylated IκB, alongside upregulation of AKT. Conclusion Propolis exhibited significant antihyperglycemic effects in db/db mice, potentially by modulating the AKT and NF-κB signaling pathways, highlighting its potential as a therapeutic agent for diabetes management.