ObjectiveTo evaluate the comprehensive intervention effects of Huangqin Qingre Chubi Capsule （黄芩清热除痹胶囊， HQC） on self-perception of patients （SPP） and immune inflammation in patients with rheumatoid arthritis （RA）， and to explore its potential mechanisms. MethodsClinical data of 452 RA patients were retrospectively collected. Patients were divided into a control group （274 cases）， treated with conventional western medicine， and an observation group （178 cases）， treated with HQC for at least 2 weeks in addition to conventional western medicine. The treatment duration was 2 weeks for both groups. Propensity score matching （PSM） was performed at a ratio of 1∶1 to match patients between groups. SPP including the Chinese version of the short form-36 health survey （SF-36）， self-rating anxiety scale （SAS）， self-rating depression scale （SDS）， visual analog scale （VAS）， and Chinese patient-reported index for rheumatoid arthritis （CPRI-RA）， as well as immune inflammatory indicators， including erythrocyte sedimentation rate （ESR）， high-sensitivity C-reactive protein （hs-CRP）， rheumatoid factor （RF）， anti-cyclic citrullinated peptide antibody （anti-CCP）， interleukin-6 （IL-6）， immunoglobulin A （IgA）， immunoglobulin G （IgG）， immunoglobulin M （IgM）， complement C3， and complement C4， were collected before and after treatment. Spearman correlation analysis was used to assess the relationships between SPP and immune inflammatory indicators. Logistic regression， association rule analysis， and mediation analysis were performed to evaluate the effects and potential pathways of HQC on SPP and immune inflammatory indicators. Network pharmacology was applied to identify the active components and core targets of HQC in the treatment of RA， followed by molecular docking verification. In cell experiments， cells were divided into normal group， model group， 20% medicated serum group， and 80 nmol/L control group. Human synovial fibroblasts （FLS） were cultured with complete medium in the normal group， while human rheumatoid arthritis fibroblast-like synoviocytes （RA-FLS） were cultured in the model group. In the 20% medicated serum group， RA-FLS were cultured with medium containing 20% HQC-medicated serum， and in the 80 nmol/L control group， RA-FLS were cultured with complete medium containing 80 nmol/L methotrexate suspension. After 48 h of culture， cell viability was detected by cell counting kit-8 （CCK-8） assay. Levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and interleukin-10 （IL-10） in the cell supernatant were measured by enzyme-linked immunosorbent assay （ELISA）. Protein levels of matrix metalloproteinase 9 （MMP9）， transcription factor AP-1 subunit （JUN）， vascular endothelial growth factor A （VEGFA）， and C-X-C motif chemokine ligand 8 （CXCL8） were detected by Western Blot， and cell migration ability was evaluated using Transwell assay. ResultsAfter PSM， 178 cases were included in each group. After treatment， SF-36 scores increased， while scores of SAS， SDS， VAS and CPRI-RA， levels of ESR， hs-CRP， IL-6， complement C3， and complement C4 levels decreased in both groups； IgG and IgM levels were also reduced in the observation group （P＜0.05）. Physical functioning （correlation coefficient -0.19， P＜0.05） and social functioning （correlation coefficient -0.18， P＜0.05） of SF-36 were negatively correlated with hs-CRP， while VAS score was positively correlated with hs-CRP （correlation coefficient 0.19， P＜0.05）. HQC showed high associations with improvements in multiple indicators of SPP and immune inflammatory， and acted as a protective factor for the improvement of several SPP； hs-CRP and ESR played partial mediating roles in the improvement of SPP induced by HQC （P＜0.05）. Network pharmacology analysis identified baicalein， quercetin， α1-sitosterol， β-sitosterol， stigmasterol， baicalin， and crocetin as the core active components， and JUN， IL-6， VEGFA， MMP9， IL-1β， and CXCL8 as the core targets. Molecular docking results showed strong binding affinities of quercetin with VEGFA， JUN， MMP9， IL-6， and IL-1β， of baicalin with VEGFA and MMP9， and of wogonin with CXCL8. Cell experiments demonstrated that HQC and methotrexate inhibited RA-FLS viability and migration， reduced levels of IL-1β， IL-6， and IL-8， decreased protein levels of MMP9， JUN， VEGFA， and CXCL8， and increased IL-10 levels （P＜0.05）. ConclusionHQC can improve SPP in RA by regulating immune inflammatory responses. Its mechanism may be related to multi-pathway and multi-target inhibition of synovial cell inflammation and migration.

Cytotoxicity, usually represented by cell viability, is a crucial parameter for evaluating drug safety in vitro. Accurate prediction of cell viability/cytotoxicity could accelerate drug development in the early stage. In this study, by integrating cellular transcriptome and cell viability data using four machine learning algorithms (support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM)) and two ensemble algorithms (voting and stacking), highly accurate prediction models of 50% and 80% cell viability were developed with area under the receiver operating characteristic curve (AUROC) of 0.90 and 0.84, respectively; these models also showed good performance when utilized for diverse cell lines. Concerning the characterization of the employed Feature Genes, the models were interpreted, and the mechanisms of bioactive compounds with a narrow therapeutic index (NTI) can also be analyzed. In summary, the models established in this research exhibit superior capacity to those of previous studies; these models enable accurate high-safety substance screening via cytotoxicity prediction across cell lines. Moreover, for the first time, Cytotoxicity Signature (CTS) genes were identified, which could provide additional clues for further study of mechanisms of action (MOA), especially for NTI compounds.

Objective To investigate the effects of STIP1 homology and U-box containing protein 1(STUB1)on the ubiquitination of glutathione peroxidase 4(GPX4)and ferroptosis in colon cancer cells HCT116,as well as the impact on CD8+T cell-mediated killing of HCT116 cells.Methods HCT116 cells were divided into control group,empty plasmid transfection(pcDNA3.1-vector)group,STUB1 overexpression plasmid transfection(pcDNA3.1-STUB1)group,and co-transfection(pcDNA3.1-STUB1+pcDNA3.1-GPX4)group.Cell proliferation ability was assessed by CCK-8 assay.Clonogenic ability was determined by clone formation assay.Malondialdehyde(MDA)levels in cells were measured using an MDA kit.Intracellular ferrous ion(Fe2+)levels were detected with an Fe2+probe.Changes in mitochondrial membrane potential were detected using JC-1 dye.Protein expression levels of STUB1,solute carrier family 7 member 11(SLC7A11),and GPX4 were determined by western blot.The binding between STUB1 and GPX4 was assessed by co-immunoprecipitation.The effect of STUB1 on GPX4 protein ubiquitination was detected using a ubiquitin antibody.HCT116 cells transfected with different plasmids were co-cultured with human peripheral blood CD8+T cells,and the killing ability of CD8+T cells against HCT116 cells was measured using a lactate dehydrogenase(LDH)kit.Perforin,granzyme,and interferon-γ levels in the co-culture supernatant were determined by ELISA.Results Compared with the control group,the pcDNA3.1-STUB1 group showed decreased cell proliferation ability,mitochondrial membrane potential,and protein expression levels of SLC7A11 and GPX4,along with increased STUB1 protein expression,MDA,Fe2+levels,and GPX4 ubiquitination in HCT116 cells.Compared with the pcDNA3.1-STUB1 group,the pcDNA3.1-STUB1+pcDNA3.1-GPX4 group exhibited increased cell proliferation ability,mitochondrial membrane potential,and expression levels of SLC7A11 and GPX4,along with decreased MDA and Fe2+levels in HCT116 cells.After co-culture of HCT116 cells with CD8+T cells,the pcDNA3.1-STUB1 group showed significantly increased killing rate of CD8+T cells against HCT116 cells,as well as elevated levels of perforin,granzyme,and interferon-γ in the co-culture supernatant compared with the control group.Compared with the pcDNA3.1-STUB1 group,the pcDNA3.1-STUB1+pcDNA3.1-GPX4 group exhibited decreased killing rate of CD8+T cells against HCT116 cells and reduced levels of perforin,granzyme,and interferon-γ in the co-culture supernatant.Conclusion Overexpression of STUB1 promotes GPX4 ubiquitination in colon cancer cells HCT116,induces ferroptosis,and enhances the killing effect of CD8+T cells on HCT116 cells.

Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.

Objective:To explore the effects of childhood trauma on resting blood pressure, heart rate, and heart rate variability in patients with depression.Methods:A cross-sectional study was designed to prospectively collect clinical data on a total of 163 patients with depression, including 47 males and 116 females, aged 18-50 years,with mean[ M( Q1, Q3)] [29.0, (21.0, 37.0)]years, who were either the outpatients or the inpatients in the Mental Health Center of the First Hospital of Hebei Medical University from September 2022 to June 2024. The Childhood Trauma Questionnaire-Short form (CTQ-SF) was used to assess the experience of abuse and neglect during childhood. According to the CTQ-SF score, the subjects were divided into a trauma group ( n=80) and a non-trauma group ( n=83). The 17-item Hamilton Depression Scale (HAMD 17) and Hamilton Anxiety Scale (HAMA) were used to assess depressive and anxiety symptoms in the participants, respectively. A digital blood pressure monitor and an autonomic nervous system response detector were employed to measure resting blood pressure, heart rate, and heart rate variability (HRV). Spearman correlation analysis was used to examine the relationships between childhood trauma and resting blood pressure, heart rate, and HRV. Multiple linear regression analysis was performed to analyze factors influencing these parameters. The Bootstrap method was employed to test the potential mediating role of parasympathetic nervous system activity in the relationships between childhood trauma and resting blood pressure, and heart rate. Results:No significant difference was observed in resting heart rate between the trauma and non-trauma groups ( P>0.05). However, the trauma group exhibited higher resting systolic and diastolic blood pressure [(123.3±9.1) mmHg (1 mmHg=0.133 kPa) vs(116.9±10.8) mmHg, (80.0±8.6) mmHg vs (77.0±8.0) mmHg; Z=4.08, 2.24, all P<0.05]. HRV indices, including the standard deviation of normal to normal interval (SDNN), root mean square of successive differences (RMSSD), total power (TP), low frequency (LF), and high frequency (HF), were significantly lower in the trauma group [25.3 (19.4, 30.4) me vs 36.3 (27.4, 49.0) ms, 18.3 (12.9, 27.2) me vs 26.2 (19.0, 38.5) ms, 6.0(5.4, 6.5)ms 2vs 7.0(6.3, 7.4)ms 2,4.4(3.7,5.3)ms 2vs 5.8(4.9,6.3)ms 2, 4.2(3.4, 5.2)ms 2vs 5.2(4.6, 6.1)ms 2, respectively; all P<0.001]. Spearman correlation analysis showed that childhood trauma experiences in patients with depression were positively correlated with resting systolic blood pressure and diastolic blood pressure ( r=0.309, 0.236; P<0.01), childhood trauma was negatively correlated with HRV (SDNN, RMSSD, TP, LF, HF) ( r=-0.264, -0.274, -0.271, -0.235, -0.279; all P<0.01). Multiple linear regression analysis showed that childhood trauma was positively correlated with resting-state systolic blood pressure and resting-state diastolic blood pressure ( β=0.305, 0.291; all P<0.001). Childhood trauma was negatively correlated with RMSSD, TP, LF, and HF( β=-0.244, -0.249, -0.233, -0.263; all P<0.01). Mediation effect analysis showed that parasympathetic activity partially mediated the relationship between childhood trauma and resting systolic blood pressure (effect size 0.04, standard error 0.02, 95% CI=0.01-0.09), accounting for 14.29% (0.04/0.28) of the total effect. Conclusion:Childhood trauma experiences are associated with elevated resting blood pressure and reduced HRV in patients with depression. Decreased parasympathetic activity partially mediates the relationship between childhood trauma and elevated resting systolic blood pressure in these patients.

Objective:To analyze the scientific research projects of health management disciplines in medical institutions in Beijing.Methods:This study was an observational study, and data was retrieved through computer between 2014 and 2023 from the scientific research data filling system of health management disciplines in medical institutions in Beijing region, which recorded the project name, project category, scientific research funding, institution, discipline, field, etc.. Excel 2016 was used to analyze the scientific research projects of health management disciplines in medical institutions in the Beijing region.Results:From 2014 to 2023, a total of 1 848 scientific research projects of health management disciplines in medical institutions in the Beijing region were initiated, with research funding of 1 204.775 million yuan. In terms of institutional categorization, they were mainly concentrated on central and municipal medical institutions, and in terms of research fields, there were 1 577 projects in Western medicine, with research funding of 1 133.240 million yuan, and 271 projects in Chinese medicine/combination of Chinese and Western medicine, with research funding of 71.535 million yuan. Cardiovascular diseases ranked first in the sub-discipline of Western medicine, and Chinese internal medicine ranked first in the sub-discipline of Chinese medicine.Conclusions:The scientific research projects of health management disciplines in medical institutions in Beijing are characterized by an imbalance in the distribution of institutions and the classification of funded sub-disciplines. The research innovation of health management in medical institutions needs to strengthen multidisciplinary cooperation and talent cultivation.

Objective To investigate the effects of STIP1 homology and U-box containing protein 1(STUB1)on the ubiquitination of glutathione peroxidase 4(GPX4)and ferroptosis in colon cancer cells HCT116,as well as the impact on CD8+T cell-mediated killing of HCT116 cells.Methods HCT116 cells were divided into control group,empty plasmid transfection(pcDNA3.1-vector)group,STUB1 overexpression plasmid transfection(pcDNA3.1-STUB1)group,and co-transfection(pcDNA3.1-STUB1+pcDNA3.1-GPX4)group.Cell proliferation ability was assessed by CCK-8 assay.Clonogenic ability was determined by clone formation assay.Malondialdehyde(MDA)levels in cells were measured using an MDA kit.Intracellular ferrous ion(Fe2+)levels were detected with an Fe2+probe.Changes in mitochondrial membrane potential were detected using JC-1 dye.Protein expression levels of STUB1,solute carrier family 7 member 11(SLC7A11),and GPX4 were determined by western blot.The binding between STUB1 and GPX4 was assessed by co-immunoprecipitation.The effect of STUB1 on GPX4 protein ubiquitination was detected using a ubiquitin antibody.HCT116 cells transfected with different plasmids were co-cultured with human peripheral blood CD8+T cells,and the killing ability of CD8+T cells against HCT116 cells was measured using a lactate dehydrogenase(LDH)kit.Perforin,granzyme,and interferon-γ levels in the co-culture supernatant were determined by ELISA.Results Compared with the control group,the pcDNA3.1-STUB1 group showed decreased cell proliferation ability,mitochondrial membrane potential,and protein expression levels of SLC7A11 and GPX4,along with increased STUB1 protein expression,MDA,Fe2+levels,and GPX4 ubiquitination in HCT116 cells.Compared with the pcDNA3.1-STUB1 group,the pcDNA3.1-STUB1+pcDNA3.1-GPX4 group exhibited increased cell proliferation ability,mitochondrial membrane potential,and expression levels of SLC7A11 and GPX4,along with decreased MDA and Fe2+levels in HCT116 cells.After co-culture of HCT116 cells with CD8+T cells,the pcDNA3.1-STUB1 group showed significantly increased killing rate of CD8+T cells against HCT116 cells,as well as elevated levels of perforin,granzyme,and interferon-γ in the co-culture supernatant compared with the control group.Compared with the pcDNA3.1-STUB1 group,the pcDNA3.1-STUB1+pcDNA3.1-GPX4 group exhibited decreased killing rate of CD8+T cells against HCT116 cells and reduced levels of perforin,granzyme,and interferon-γ in the co-culture supernatant.Conclusion Overexpression of STUB1 promotes GPX4 ubiquitination in colon cancer cells HCT116,induces ferroptosis,and enhances the killing effect of CD8+T cells on HCT116 cells.

Objective To investigate the association between body roundness index(BRI)and hyperuricemia(HUA)in patients with type 2 diabetes mellitus(T2DM).Methods 555 T2DM inpatients were selected from July 2022 to October 2023 in Gansu Province People's Hospital Endocrinology.According to BRI,the T2DM patients were divided into four group:low BRI(L-BRI,BRI≤3.579,n=140)group,moderate BRI(M-BRI,3.579

Objective To analyze the risk factors of delayed bleeding after colonic polyp resection.Methods 700 patients with colonic polyps admitted to General medical treatment Hanzhong 3201 hospital from January 2022 to May 2023 were included as the research object,and all patients were treated with colonoscopy polypectomy.According to whether Post-procedural bleeding(PPB)occurred after operation,they were divided into two groups:the group with PPB occurrence(n=85 cases)and the group without PPB occurrence(n=615 cases).The general data,clinical data and operation-related data of the two groups were analyzed by univariate analysis.Multivariate Logistic regression was used to analyze the risk factors of postoperative PPB,and receiver operating characteristic curve was drawn to analyze the predictive value of risk factors.Results 700 patients in this study were all treated by colon polypectomy,and 85 patients(12.14％)developed PPB within 30 days after operation,that is,the incidence of PPB in this study was 12.14％.There was significant difference in sex,age,hypertension and treatment history of thrombosis between the two groups(P＜0.05).There was significant difference in the morphology,diameter and surgical methods between the two groups(P＜0.05).Multivariate Logistic regression analysis showed that polyp morphology(stalk),polyp diameter(＞1 cm),Endoscopic mucosal resection(EMR)and Endoscopic submucosal dissection(ESD)were the risk factors for postoperative PPB(P＜0.05).The ROC curve showed that the area under curve of polypoid-shaped is 0.653,95％CI is 0.616-0.688,the AUC of polyp-diameter is 0.741,95％CI is 0.707-0.773;and in the way of operation,the AUC of argon plasma coagulation/ESD is 0.730,95％CI is 0.713-0.802,the AUC of EMR/ESD is 0.541,95％CI is 0.498-0.584,the AUC of APC/EMR is 0.604 and 95％CI is 0.565-0.641.Conclusion Polyp pedicled,diameter＞1 cm,EMR and ESD are the risk factors for postoperative PPB.

Objective To investigate the effects of obesity-related indexes on cardiovascular autonomic nervous function in type 2 diabetes mellitus(T2DM)patients.Methods A total of 421 T2DM patients treated in the Department of Endocrinology of Gansu Provincial People's Hospital were enrolled in this study from October 2020 to October 2023.All the patients were divided into simple T2DM group with VFA<100 cm2(n=193)and obese group with VFA≥100 cm2(OB,n=228)according to visceral fat area(VFA).BMI,waist-to-height ratio(WHtR),waist-to-hip ratio(WHR),lipid accumulation index(LAP),visceral fat index(VAI),Chinese visceral fat index(CVAI),tapeness index(CI),body shape index(ABSI),and body roundness index(BRI)were calculated.Time domain parameters of heart rate variability(HRV)in 24 h holter electrocardiogram were recorded,including the global standard deviation(SDNN)of normal sinus RR interval,standard deviation of mean value of sinus RR interval(SDANN),root mean square difference(RMSSD)of normal continuous sinus RR interval.The percentage of adjacent RR interval difference>50 ms in total interval(PNN50),the HRV triangle index,the standard deviation of the difference of the entire adjacent NN interval length(SDSD).Results Compared with T2DM group,the OB group showed an increase in age,weight,BMI,WC,hip circumference(HC),neck circumference(NC),SBP,HbA1c,TG,SUA,CI,WHtR,WHR,VFA,SFA,VAI,LAP,CVAI,and BRI(P<0.05 or P<0.01),while a decrease in HDL-C(P<0.05).The SDNN,SDANN,SDSD,RMSSD,HRV trigonometric index,and PNN50 were lower in OB group than in T2DM group(P<0.05 or P<0.01).Spearman correlation analysis showed that SDNN and HRV trigonometric index was negatively correlated with age,DM duration,HR,SBP,PWV,WHtR,TG,SUA,VAI,LAP,BRI,VFA,LAP,and CVAI(P<0.05 or P<0.01).Logistic regression analysis shows that age,VFA,and LAP are influencing factors for cardiac autonomic dysfunction.The analysis of the working characteristic curve of the subjects showed that the area under the curve of VFA,age,and LAP in predicting cardiovascular autonomic dysfunction was 0.680,0.614,and 0.577,with sensitivity of 87.5%,41.7%,and 61.8%,and specificity of 47.3%,73.6%,and 55.6%respectively.Conclusions BMI,HC,NC,WC,TG,SFA,CI,WHtR,WHR,LAP,BRI,VAI,CVAI and VFA are closely related to cardiovascular autonomic nervous function in T2DM patients.As VFA,Ageand LAP increase,the risk of cardiovascular autonomic dysfunction increases.