Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

Objective:To explore the differences in sociodemographic and clinical characteristics between pa-tients with unipolar depression bipolar depression and to establish a nomogram for identifying bipolar depression.Methods:Using data from the China Mental Disorders Cohort Study,the sociodemographic and clinical characteristics of 2 643 patients with unipolar depression and 250 patients with bipolar depression diagnosed accord-ing to the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)were includ-ed to compare their sociodemographic and clinical characteristics.These characteristics included general demograph-ic information,disease-related information,clinical examination results,and the severity of the disease assessed with the Global Assessment of Functioning(GAF)and Hamilton Depression Rating Scale.Logistic regression analysis was employed to identify factors influencing bipolar depression,and a nomogram was constructed for its identifica-tion.Results:The risk factors for bipolar depression included being male(OR=1.48),being employed(OR=1.38),having non-melancholic features during episodes(OR=2.33),a Body Mass Index ranging from normal to obese(OR=2.48,2.49,4.65),psychotic features(OR=2.14),mixed episode(OR=9.36),comorbid physical diseases(OR=2.47),four or more depressive episodes(OR=1.67),earlier age of onset(OR=0.95),longer ill-ness duration(OR=1.03),and higher GAF scores(OR=1.02).The nomogram model achieved an AUC of 0.81(95％CI:0.78-0.84).The Hosmer-Lemeshow test result was x2=6.96(P＞0.05),indicating good model fit.The calibration curve showed good performance.The decision curve analysis revealed that the nomogram pro-vides significant clinical benefit when the risk of bipolar depression was within the range of 0 to 0.9.Conclusion:The nomogram established based on the identified sociodemographic and clinical factors can accurately assess the risk of bipolar depression,providing a useful tool for early identification and intervention.

Objective:To explore the effect of different types of social activity participation on self-rated men-tal health disparity between urban and rural older adults in China.Methods:The study data was sourced from the 2018 wave of Chinese General Social Survey(CGSS).Factor analysis was applied to divide social activities into three dimensions:entertainment activities,cultural activities,family and friend gatherings.Logistic regression model was adopted to analyze the effect of social activity on self-rated mental health.Fairlie decomposition model was ap-plied to explore the effect of social activity on urban-rural disparity in self-rated mental health.Results:The self-ra-ted good mental health proportion of urban old persons(n=3 139)was 72.0％,which was higher than that of rural old persons(n=1 549)(53.7％)(P＜0.001).Recreational activities and gatherings of friends and relatives sig-nificantly improved self-rated mental health in urban and rural old persons.Fairlie decomposition result revealed that approximately 18.7％of self-rated mental health disparity could be attributed to urban-rural disparity in entertain-ment activities.Moreover,urban-rural disparity in family and friends gatherings could explain about 3.9％of the disparity.Conclusion:Urban older adults have better mental health than their rural counterparts.Furthermore,social activity is beneficial to mental health for both urban and rural older adults.Urban-rural disparity in entertainment ac-tivities make an important contribution to mental health disparity between urban and rural older adults.

Objective:To explore the differences in sociodemographic and clinical characteristics between pa-tients with unipolar depression bipolar depression and to establish a nomogram for identifying bipolar depression.Methods:Using data from the China Mental Disorders Cohort Study,the sociodemographic and clinical characteristics of 2 643 patients with unipolar depression and 250 patients with bipolar depression diagnosed accord-ing to the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)were includ-ed to compare their sociodemographic and clinical characteristics.These characteristics included general demograph-ic information,disease-related information,clinical examination results,and the severity of the disease assessed with the Global Assessment of Functioning(GAF)and Hamilton Depression Rating Scale.Logistic regression analysis was employed to identify factors influencing bipolar depression,and a nomogram was constructed for its identifica-tion.Results:The risk factors for bipolar depression included being male(OR=1.48),being employed(OR=1.38),having non-melancholic features during episodes(OR=2.33),a Body Mass Index ranging from normal to obese(OR=2.48,2.49,4.65),psychotic features(OR=2.14),mixed episode(OR=9.36),comorbid physical diseases(OR=2.47),four or more depressive episodes(OR=1.67),earlier age of onset(OR=0.95),longer ill-ness duration(OR=1.03),and higher GAF scores(OR=1.02).The nomogram model achieved an AUC of 0.81(95％CI:0.78-0.84).The Hosmer-Lemeshow test result was x2=6.96(P＞0.05),indicating good model fit.The calibration curve showed good performance.The decision curve analysis revealed that the nomogram pro-vides significant clinical benefit when the risk of bipolar depression was within the range of 0 to 0.9.Conclusion:The nomogram established based on the identified sociodemographic and clinical factors can accurately assess the risk of bipolar depression,providing a useful tool for early identification and intervention.

Objective:To explore the effect of different types of social activity participation on self-rated men-tal health disparity between urban and rural older adults in China.Methods:The study data was sourced from the 2018 wave of Chinese General Social Survey(CGSS).Factor analysis was applied to divide social activities into three dimensions:entertainment activities,cultural activities,family and friend gatherings.Logistic regression model was adopted to analyze the effect of social activity on self-rated mental health.Fairlie decomposition model was ap-plied to explore the effect of social activity on urban-rural disparity in self-rated mental health.Results:The self-ra-ted good mental health proportion of urban old persons(n=3 139)was 72.0％,which was higher than that of rural old persons(n=1 549)(53.7％)(P＜0.001).Recreational activities and gatherings of friends and relatives sig-nificantly improved self-rated mental health in urban and rural old persons.Fairlie decomposition result revealed that approximately 18.7％of self-rated mental health disparity could be attributed to urban-rural disparity in entertain-ment activities.Moreover,urban-rural disparity in family and friends gatherings could explain about 3.9％of the disparity.Conclusion:Urban older adults have better mental health than their rural counterparts.Furthermore,social activity is beneficial to mental health for both urban and rural older adults.Urban-rural disparity in entertainment ac-tivities make an important contribution to mental health disparity between urban and rural older adults.

Objective:To describe the detail sampling design,weighting,instruments,filed procedures and quality control methods of the epidemiological survey on dementia among community residents in Tongliao City.Methods:A three-stage disproportionate probability sampling design was used to investigate the inhabitants aged 65 years and over in Tongliao City,Inner Mongolia Autonomous Region.The 10/66 Dementia Research Group(10/66 DRG)assessment instruments were used to diagnose dementia,using computer-assisted personal interview mode in the selected older people.Comprehensive quality control methods were implemented throughout the field-work.Results:A total of 166 villages or communities were sampled from nine counties or districts in Tongliao Cit-y.Totally 4 345 older people were interviewed with 96.2％response rate.By calculating sampling design weights,non-response adjustment weights and post-stratification adjustment weights,these weights were multiplied and per-formed trimming adjustment and standardization adjustment to generate final weights.The 171 interviewers were well-trained and qualified to carry out filed interview.Quality control methods included computer data check,audio record check,and telephone check in order to ensure the quality of the survey.Conclusion:This survey is imple-mented using a rigorous sampling design and timely quality control methods,and uses the 10/66 DRG assessment instruments with satisfactory international validity and reliability as survey instruments,which has international cross-cultural comparability.It provides a valid and feasible methodology of epidemiological survey on dementia for further studies in different regions in China.

Objective:To estimate the costs of dementia from a societal perspective in Tongliao City and ex-plore the influencing factors of these costs.Methods:Dementia was diagnosed using the 10/66 Dementia Research Group assessment instruments.Data on healthcare utilization,caregiver's care time or costs,and the distress due to caregiving were collected.The cost-proportion conversion method was used to estimate the per capita cost of health services based on data from the National Statistical Yearbook.The human capital approach was used to estimate the unit value of informal care time,and the willingness-to-pay method was used to measure the intangible costs of car-egivers.The total societal costs of dementia were calculated based on the reference year 2023,and a two-part model was employed to analyze the factors influencing the societal costs.Results:A total of 390 dementia patients were di-agnosed,with an average societal cost per capita of 117 877 Yuan.The largest cost component was informal care provided by unpaid family members,accounting for 73.1％of the total societal cost.The societal costs for female patients were 61 395 Yuan higher than those for male patients.Patients with comorbid stroke had a higher societal cost of 63 008 Yuan compared to patients without stroke,and each additional chronic disease added 5 868 Yuan to societal costs.Additionally,each non-memory dimension impairment in the Clinical Dementia Rating Scale in-creased the societal costs by 53 997 Yuan.Conclusion:Dementia poses a significant socio-economic burden,with informal care being the major component of this burden.

Objective:To compare clinical characteristics,treatment patterns and physiological indicators in bipolar disorder(BD)patients with different age of onset.Methods:Totally 380 patients with DSM-5 BD were se-lected in this study.Psychiatrists diagnosed the patients using the Mini International Neuropsychiatric Interview.The clinical information questionnaire and the Global Assessment of Functioning scale were utilized to collected clinical characteristics,treatment status,and physiological indicators.The onset age of BD was divided into 21 and 35 years as cut-off points.Multivariate logistic regression and linear regression were used to analyze related factors.Results:Among the 380 patients with BD,199 cases were early-onset group(52.4％),121 cases were middle-onset group(31.8％),and 60 cases were late-onset group(15.8％).There were 26.6％of patients in the early-onset group in-itially diagnosed as depression,23.1％in the middle-onset group,and 11.7％in the late-onset group.Multivariate analysis revealed that compared to the early-onset group of BD,the middle-onset(OR=2.22)and late-onset(OR=4.99)groups had more risk to experience depressive episodes,and the late-onset group(OR=6.74)had 6.74 times of risk to suffer from bipolar Ⅱ disorder.Additionally,patients in the middle-onset(β=-1.52)and late-on-set(β=-4.29)groups had shorter durations of delayed treatment,and those in the middle-onset(β=-1.62)and late-onset(β=-3.14)groups had fewer hospitalizations.Uric acid levels were lower in both the middle-onset(β=-28.39)and late-onset(β=-31.47)groups,and total cholesterol level was lower in the middle-onset group(β=-0.23).Conclusion:Patients with BD in different age of onset show significant differences in clinical charac-teristics,treatment conditions and physiological indicators.

RNA modifications affect many biological processes and physiological diseases. The 5-methylcytosine (m⁵C) modification regulates the progression of multiple tumors. However, its characteristics and functions in hepatocellular carcinoma (HCC) remain largely unknown. Here, we found that HCC tissues had a higher m⁵C methylation level than the adjacent normal tissues. Transcriptome analysis revealed that the hypermethylated genes mainly participated in the phosphokinase signaling pathways, such as the Ras and PI3K-Akt pathways. The m⁵C methyltransferase NSUN2 was highly expressed in HCC tissues. Interestingly, the expression of many genes was positively correlated with the expression of NSUN2, including GRB2, RNF115, AATF, ADAM15, RTN3, and HDGF. Real-time PCR assays further revealed that the expression of the mRNAs of GRB2, RNF115, and AATF decreased significantly with the down-regulation of NSUN2 expression in HCC cells. Furthermore, NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling pathway. Moreover, knocking down NSUN2 caused cell cycle arrest. Taken together, our study demonstrates the vital role of NSUN2 in the progression of HCC.
Humans ; ADAM Proteins ; Apoptosis Regulatory Proteins ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Membrane Proteins ; Methyltransferases/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Repressor Proteins ; RNA, Messenger/metabolism* ; Sorafenib ; RNA Methylation/genetics*

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) positively affect the initial control of non-small cell lung cancer (NSCLC). Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment. However, the mechanisms that control the resistance of EGFR-TKIs remain largely unknown. RNA structures have widespread and crucial functions in many biological regulations; however, the functions of RNA structures in regulating cancer drug resistance remain unclear. Here, the psoralen analysis of RNA interactions and structures (PARIS) method is used to establish the higher-order RNA structure maps of EGFR-TKIs-resistant and -sensitive cells of NSCLC. Our results show that RNA structural regions are enriched in untranslated regions (UTRs) and correlate with translation efficiency (TE). Moreover, yrdC N⁶-threonylcarbamoyltransferase domain containing (YRDC) promotes resistance to EGFR-TKIs. RNA structure formation in YRDC 3' UTR suppresses embryonic lethal abnormal vision-like 1 (ELAVL1) binding, leading to EGFR-TKI sensitivity by impairing YRDC translation. A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide (ASO) to perturb the interaction between RNA and protein. Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; ErbB Receptors/metabolism* ; GTP-Binding Proteins/therapeutic use* ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; RNA ; RNA-Binding Proteins/genetics* ; Tyrosine Kinase Inhibitors/therapeutic use*