ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5％(2 576/4 479)]was higher than that of female patients[42.5％(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0％(2 241/4 479)].About 90.0％of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6％of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5％of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8％.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6％).98.6％of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.

Objective:To evaluate the role of NOD-like receptor protein 3 (NLRP3) inflammasome-mediated microglia activation in myocardial ischaemia-reperfusion-induced brain injury in mice.Methods:Fifty-two SPF healthy male wild-type C57BL/6 mice and 52 NLRP3 -/- mice, aged 8-10 weeks, were divided into 4 groups ( n=26 each) using a random number table method: wild type sham operation group (W-S group), wild type myocardial ischemia-reperfusion group (W-IR group), NLRP3 -/- sham operation group (NLRP3 -/--S group), and NLRP3 -/- myocardial ischemia-reperfusion group (NLRP3 -/--IR group). The myocardial ischemia-reperfusion-induced brain injury model was established by ligating the left anterior descending coronary artery for 45 min followed by 24 h of reperfusion in anesthetized mice. The cognitive function was evaluated using the modified Morris water maze test at 24 h of reperfusion. The mice were sacrificed after blood specimens were collected, and brain tissues were obtained for measurement of the blood-brain barrier permeability and water content, for microscopic examination of the pathological changes of brain tissues, and for determination of serum S-100β protein and neuron-specific enolase (NSE) concentrations, contents of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in hippocampal tissues (by enzyme-linked immunosorbent assay), expression of NLRP3, apoptosis-associated speck-like protein (ASC), cleaved cysteine aspartate protease 1 (cleaved-caspase-1), gasdermin D (GSDMD), ionized calcium-binding adapter molecule 1 (Iba-1), and occludin in hippocampal tissues (by immunofluorescence and/or Western blot). The apoptosis rate of neurons and density of dendritic spine were calculated. Results:Compared with sham operation group, the escape latency was significantly prolonged, the number of crossing the original platform was decreased, and the time spent in the target quadrant was shortened, the concentrations of serum S-100β protein and NSE were increased, the blood-brain barrier permeability and brain water content were increased, the dendritic spine density in the hippocampal CA1 area was decreased, the contents of IL-1β, IL-6 and TNF-α were increased, the expression of NLRP3, ASC, cleaved-caspase-1, GSDMD and Iba-1 was up-regulated, and the expression of occludin was down-regulated ( P<0.05), and the pathological injury to brain tissues was found in ischemia-reperfusion group. Compared with W-IR group, the escape latency was significantly shortened, the number of crossing the original platform was increased, and the time spent in the target quadrant was prolonged, the concentrations of serum S-100β protein and NSE were decreased, the blood-brain barrier permeability and brain water content were decreased, the dendritic spine density in the hippocampal CA1 area was increased, the contents of IL-1β, IL-6 and TNF-α were decreased, the expression of NLRP3, ASC, cleaved-caspase-1, GSDMD and Iba-1 was down-regulated, and the expression of occludin was up-regulated ( P<0.05), and the pathological injury to brain tissues was alleviated in NLRP3 -/--IR group. Conclusions:NLRP3 inflammasome-mediated microglia activation is involved in myocardial ischaemia-reperfusion-induced brain injury in mice.

Objective To analyze the latent classes of social alienation in colorectal cancer patients and further explore the influencing factors and cumulative effects of risk factors across different classes,thereby providing a reference for individualized interventions.Methods Convenience sampling was used to select colorectal cancer patients hospitalized in the gastrointestinal surgery and oncology departments of 3 tertiary-level hospitals in Shandong Province from January to June 2023 as the study subjects.A questionnaire survey was conducted using the General Information Questionnaire,Social Avoidance Scale,Social Anxiety Scale,UCLA Loneliness Scale,Sense of Coherence Scale,Family Cohesion Scale,and Social Support Rating Scale.Data analysis was performed using latent profile analysis and multivariate logistic regression analysis.Results A total of 292 questionnaires were distributed,with 270 valid responses collected,yielding a response rate of 92.47％.The results of the latent profile analysis indicated that social alienation among colorectal cancer patients could be categorized into 3 latent groups:the"low alienation group"(42.59％),the"high alienation-high social avoidance group"(14.08％),and the"moderate alienation-high social anxiety group"(43.33％).Results of logistic regression analysis revealed that employment status,stoma status,metastasis,sense of coherence,family cohesion,and social support were influencing factors across different categories.Moreover,a cumulative effect of sense of coherence,family cohesion,and social support on distinct categories was observed(P＜0.05).Conclusion Social alienation among colorectal cancer patients exhibits group heterogeneity.Healthcare professionals should identify the characteristic differences among patients,prioritise those with multiple risk factors,and develop targeted intervention measures to help them better integrate into society.

Objective To investigate the effects and mechanisms of Huatan Quyu Decoction on learning and memory abilities in rats with vascular dementia(VD).Methods Totally 112 male SD rats were randomly selected with 16 rats as the sham-operation group,the remaining rats were used to prepare VD models by segmental ligation of the common carotid artery.The successfully modeled rats were randomly divided into model group,Huatan Quyu Decoction low-,medium-and high-dosage groups(6.1,12.1,24.2 g/kg),donepezil hydrochloride group(0.5 mg/kg)and combination group(Huatan Quyu Decoction 12.1 g/kg+donepezil hydrochloride 0.5 mg/kg),with 16 rats in each group.Each group was given the corresponding treatment measures for 4 weeks.The Morris water maze test was used to assess learning and memory abilities,neurological function was evaluated using Garcia score,HE staining was used to observe the morphology of the hippocampal tissue,ELISA was employed to detect the serum content of Aβ,immunohistochemistry was utilized to observe the β-catenin,LRP6 and GSK-3β protein expression in brain tissue.Results Compared with the sham-operation group,the escape latency of the model group rats was prolonged(P<0.01),the number of crossing platforms was reduced(P<0.01),and the neurological deficit score was decreased(P<0.01),the arrangement of hippocampal tissue cells was disorderly,and the tissue was severely damaged,the serum Aβ content increased(P<0.01),the expressions of β-catenin and LRP6 protein in brain tissue decreased,and the expression of GSK-3β protein increased(P<0.01).Compared with the model group,the escape latency of rats in each administration group was shortened,the number of crossing platforms increased,the neurological deficit score increased,the number of hippocampal cells was relatively more,the arrangement was more orderly,and the structure was relatively complete,the serum Aβ content decreased,the expressions of β-catenin and LRP6 proteins increased,and the expression of GSK-3β protein decreased.Among them,Huatan Quyu Decoction high-dosage group had a significantly better effect than Huatan Quyu Decoction low-and medium-dosage groups(P<0.01),and there was no statistical significance in various indicators compared with the donepezil hydrochloride group(P>0.05).Compared with the donepezil hydrochloride group,the combination group showed significant improvements in learning and memory abilities(P<0.01),the neurological deficit score significantly increased(P<0.01),the number of hippocampal cells significantly increased,arranged neatly,and structurally intact,the serum Aβ content significantly decreased(P<0.01),the expression of β-catenin and LRP6 proteins significantly increased,and the expression of GSK-3β protein significantly decreased(P<0.01).Conclusion Huatan Quyu Decoction can repair cognitive function in VD rats,improve learning and memory abilities,and alleviate VD symptoms by activating the Wnt/β-catenin signaling pathway to reduce serum Aβ content,decrease the apoptosis of nerve cells and alleviate the degree of pathological damage in hippocampal tissue.

Objective To explore the association of the TSLP gene polymorphisms at rs3806932,rs11466741 and rs2289278 loci with childhood asthma and serum TSLP levels,and to analyze the effects of gene-environment interactions on asthma risk in children.Methods A total of 145 children with asthma and 108 healthy controls were included.Genotyping was performed using KASP and MassARRAY SNP technologies,and serum TSLP levels were measured by ELISA.Differences in allele and genotype frequencies between the two groups were analyzed,along with the impact of genetic models on asthma risk.Differences in serum TSLP levels across groups were compared.Linkage disequilibrium and haplotype analysis were performed using Haploview 4.2,and GMDR 0.9 software was used to assess gene-environment interactions.Results No significant differences were found in the allele and genotype frequencies of the three TSLP gene loci between the two groups(P＞0.05).Under the co-dominant model,children with the AG genotype at the rs3806932 locus had 1.750 times the risk of developing asthma compared to those with the AA genotype(95％CI:1.018-3.010,P=0.043).Under co-dominant and overdominant models,children with the CT genotype at the rs11466741 locus had 1.705 times the asthma risk compared to those with the CC genotype(95％CI:1.006-2.891,P=0.048),and 1.698 times the risk compared to those with the CC-TT genotype(95％CI:1.019-2.827,P=0.041).Serum TSLP levels were significantly higher in asthma patients with the CT genotype than those with the CC genotype at the rs11466741 locus(P=0.032).Serum TSLP levels were higher in the asthma group with allergic rhinitis(AR)compared to the group without AR(P＜0.01).No significant differences were observed in the distribution of haplotypes frequencies(AC,GT,GC)between the two groups(P＞0.05).GMDR analysis showed that the highest asthma risk was observed in children with heterozygous genotypes(CT,AG)at both rs11466741 and rs2289278,or those with the CT genotype at rs11466741,a history of passive smoking,and a cesarean section delivery(P＜0.05).Conclusion Polymorphisms in the TSLP gene at rs3806932 and rs11466741 are associated with an increased risk of childhood asthma.Variants at the rs11466741 locus affect serum TSLP levels in children with asthma.Asthma combined with AR leads to elevation of serum TSLP levels.The interaction between rs11466741 and rs2289278,along with environmental factors(passive smoking and cesarean section),contributes to the increase of asthma risk in children.

Objective:To investigate the prevalence of and risk factors associated with Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and high-risk human papillomavirus (HPV) coinfections among patients with newly diagnosed syphilis at a hospital in Nanjing. Methods:A cross-sectional study was conducted on patients with newly diagnosed syphilis at the STD Clinic, Hospital of Dermatology, Chinese Academy of Medical Sciences in Nanjing, China from May 2023 to April 2024. Urethral, cervical or rectal swabs were collected according to the gender and types of sexual behavior of the patients. Screening tests for CT, NG and HPV infections were then performed by nucleic acid amplification testing. High-risk HPV testing was performed only in female patients. Univariate analysis was carried out to investigate risk factors associated with CT infection. The chi-square test, chi-square test with continuity correction, or Fisher's exact test was chosen based on the sample size and expected values.Results:A total of 111 newly diagnosed syphilis patients with test specimens were collected, including 71 males (64%) and 40 females (36%), and their ages ranged from 16 to 87 years; there were 82 patients with early syphilis and 29 with late latent syphilis; the number of sexual partners in the past 3 months ranged from 0 to 3. Among the 60 male patients with early syphilis, 1 (1.7%) was co-infected with NG, and 12 (20%) with CT; among the 16 men who have sex with men, 7 (43.8%) were co-infected with CT, while 5 (11.4%) of the 44 heterosexual patients were co-infected with CT, showing a significant difference in CT infection rates between the two groups ( χ2 = 5.80, P = 0.016). Among the 22 female patients with early syphilis, 1 (4.5%) was co-infected with NG, and 8 (36.4%) with CT; among the 12 female patients aged < 25 years, 8 (66.7%) were infected with CT, while none of the 7 patients aged 25-44 years or the 3 patients aged ≥ 45 years were infected with CT, showing a significant difference in CT infection rates among the 3 age groups ( P = 0.005) ; among the 16 female patients with 1 sexual partner in the past 3 months, 3 were infected with CT, while 5 were infected with CT in the 6 female patients with 2-3 sexual partners in the past 3 months, with a significant difference in CT infection rates between the two groups ( P = 0.011). Out of the 40 female patients with syphilis, 16 (40%) were co-infected with high-risk HPV; the HPV infection rates did not differ among different age groups (age groups of < 25 years, 25-44 years, ≥ 45 years: 8/14, 2/9, 6/17, respectively; P = 0.265) . Conclusion:The CT infection rate was relatively high in patients with newly diagnosed early syphilis, and a relatively high infection rate of high-risk HPV was observed in female patients with syphilis aged < 25 years.

Objective To observe the value of T2 mapping for quantitatively evaluating the changes of junctional zone and outer myometrium caused by endometrial fibrosis.Methods A total of 73 infertility patients with endometrial fibrosis confirmed by hysteroscopy(disease group)and 33 healthy women of childbearing age(control group)were prospectively enrolled,and MR examinations were performed at the late proliferative phase of endometrium.The thickness and T2 value of junctional zone,T2 value of outer myometrium on anterior,posterior and fundus wall of midsagittal corpus uteri were measured,and the mean value of the above measurements on the three walls were calculated.Receiver operating characteristic curves were constructed,the areas under the curves(AUC)were calculated to explore the efficacy of those with significant difference among the mean thickness and the mean T2 value of junctional zone,the mean T2 value of outer myometrium and their combination for evaluating endometrial fibrosis.Results The thickness and T2 value of anterior wall,posterior wall,fundus wall and the mean junctional zone in disease group were all significantly higher than those in control group(all P＜0.001).No significant difference of T2 value of anterior wall,posterior wall,fundus wall nor the mean outer myometrium was found between groups(all P＞0.05).The mean thickness and the mean T2 value of junctional zone and their combination could be used to effectively evaluate endometrial fibrosis,with AUC of 0.839,0.822 and 0.922,respectively,and their combination had the best performance(both P＜0.01).Conclusion T2 mapping could be used to quantitatively evaluate the injury of junctional zone caused by endometrial fibrosis.

The classical latent structure method does not consider the influence of primary and secondary symptoms,syndromes and symptoms in the analysis and modeling of syndromes.In this paper,based on the data of damp-heat in intestine and stomach syndrome involving 1087 diabetic patients,the classical latent structure analysis was used to obtain the quantitative syndrome diagnostic rules.Then,using Constrained Latent Tree Analysis(CLTA),the quantitative syndrome diagnostic rules containing primary and secondary symptoms were obtained as follows,primary symptoms include halitosis(2.3),yellow tongue coating(2),abdominal distension(2.3),greasy tongue coating(2.1),loose stool or loose stool(1.5),red tongue(1.3),smooth pulse(1.4).Secondary symptoms include epigastric distension(1.1).Compared with the traditional latent structure analysis method,the rules established by CLTA are more compatible with the concept of differentiating primary and secondary symptoms and the common practice of TCM.The quantitative syndrome diagnostic rules of damp-heat in intestine and stomach syndrome constructed by the CLTA method have considerable objectivity in the modeling process.The diagnostic rules established were also compatible with the qualitative concept of TCM theory in stratifying primary and secondary symptoms.Finally,the diagnostic rules are obtained by logistic regression analysis,and the accuracy of the three rules is compared.The results show that the rule recognition accuracy obtained by CLTA is the highest.Therefore,the syndrome diagnostic rules of damp-heat in intestine and stomach obtained from the analysis of CLTA are in line with the constraint semantics of primary and secondary diseases and the theory of traditional Chinese medicine.

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.