Intervertebral disc degeneration （IVDD） is the core cause of chronic low back pain， which severely impairs patients’ quality of life and imposes a heavy social and medical burden. The hypoxia-pyroptosis-inflammation cascade mediated by hypoxia-inducible factor-1α （HIF-1α） is the core pathological mechanism driving the initiation and progression of IVDD. Natural active ingredients derived from traditional Chinese medicine （TCM） have become a research hotspot in the field of IVDD prevention and treatment due to their advantages of multi-target effects， favorable efficacy， and low toxicity. This paper systematically reviews the mechanism of HIF-1α-mediated hypoxia-pyroptosis-inflammation cascade in degenerative nucleus pulposus tissue and the intervention of related active ingredients. It is found that natural active ingredients such as baicalein， curcumin and resveratrol can intervene in the HIF-1α-mediated pathological cascade through four core links to delay IVDD progression： targeting the HIF-1α oxygen sensing pathway to block the initiation of pyroptosis cascade， inhibiting NOD-like receptor protein 3 inflammasome activation to cut off the cascade amplification of inflammatory signals， intervening in the Gasdermin D-mediated pyroptosis execution stage to protect cell membrane integrity， and regulating extracellular matrix metabolism to reconstruct intervertebral disc homeostasis.

The 5-hydroxytryptamine 2A receptor (5-HT_2AR) is one of the key targets in the development of novel antidepressants. To develop new antidepressants targeting the 5-HT_2A receptor, this study established a high-throughput screening method for drugs targeting the 5-HT_2A receptor based on the principle of detecting calcium flux signals. The immunofluorescence assay and western blotting were employed to evaluate receptor expression levels in the 5-HT_2AR-CHO cell line. The reaction system parameters, including cell seeding density, DMSO concentration, and dye incubation time, were optimized with Z'-factor and signal window values as evaluation indicators. The specificity, precision, stability, and applicability of the method were assessed. Results indicated that the 5-HT_2AR-CHO cell line stably expressed high levels of the 5-HT_2A receptor. The optimized screening method involved a reaction system with 10 000 cells/well, 0.2% DMSO, and 2 h incubation with Calcium 6 dye. The method demonstrated excellent specificity, with inter-batch precision below 10% for the detection of 5-hydroxytryptamine (5-HT) at low, medium, and high concentrations. Testing four compounds that target the 5-HT_2A receptor- agonists 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD), along with the antagonist MDL100907-yielded Z'-factors (at EC₈₀) greater than 0.85 and signal window values over 0.91. The EC₅₀ values of these compounds were in the nanomolar range, and their potency rank order aligned with previously reported data, confirming the reliability of the established method. When being applied to the detection of 38 known active compounds, the method efficiently identified 5-HT_2A receptor agonists and antagonists while showing no response to non-target compounds. In conclusion, this study successfully constructs a high-throughput screening approach for 5-HT_2A receptor-targeting drugs based on calcium flux signals. The method possesses strong specificity, high sensitivity, and robust stability, being suitable for screening antidepressants targeting the 5-HT_2A receptor.
High-Throughput Screening Assays/methods* ; Receptor, Serotonin, 5-HT2A/metabolism* ; Animals ; CHO Cells ; Cricetulus ; Calcium Signaling/drug effects* ; Antidepressive Agents/pharmacology* ; Humans ; Serotonin 5-HT2 Receptor Antagonists/pharmacology* ; Calcium/metabolism*

OBJECTIVE To investigate the efficacy and safety of metformin in the treatment of diabetes mellitus type 2 （T2DM） complicated with sarcopenia in elderly patients. METHODS From January 2022 to January 2024， clinical data from eligible patients with T2DM complicated with sarcopenia treated at the First Affiliated Hospital of Chongqing Medical and Pharmaceutical College were collected. Patients were randomly assigned into control group （70 cases） and observation group （70 cases） using a random number table. Both groups received routine interventions； control group additionally received subcutaneous injections of Insulin glargine injection before bedtime and Human insulin injection 30 minutes before breakfast， lunch and dinner every day. In addition to the same treatments as the control group， the observation group was administered 0.5 g of Metformin hydrochloride sustained-release tablets orally once daily. Both groups were treated continuously for 24 weeks. Comparisons were made between the two groups in terms of glucose metabolism indexes [fasting blood glucose （FBG）， 2 h postprandial blood glucose （2 hBG）， and glycosylated hemoglobin （HbA1c）]， homeostasis model assessment of insulin resistance （HOMA-IR）， appendicular skeletal mass muscle index （ASMI）， grip strength， walking speed， lipid metabolism indexes [serum total triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）]， serological markers [high-sensitivity C reactive protein （hs-CRP）， interleukin-6 （IL-6）， and ferritin levels] and quality of life. The occurrence of ADR was recorded in both groups. RESULTS 65 patients in the control group and 63 patients in the observation group completed this study， respectively. After treatment， the levels of FBG， 2 hBG， HbA1c， HOMA-IR，TG and TC in both groups， and the levels of hs-CRP， IL-6 and ferritin in observation group were all significantly reduced compared to those before treatment （P＜0.05）， and the HOMA-IR in observation group was significantly lower than control group （P＜0.05）； additionally， the grip strength， walking speed， and scores for daily living and activity abilities of observation group were increased than those before treatment and the control group （P＜0.05）. The incidence of adverse drug reactions in both groups was 2.86%. CONCLUSIONS Metformin can reduce inflammatory factors and ferritin levels， promote the recovery of muscle mass and strength， improve insulin resistance， and quality of life in elderly patients with T2DM complicated with sarcopenia， and does not increase the occurrence of adverse drug reactions.

Objective:To explore the association between childhood trauma and prefrontal cortex functional networks in early adulthood using functional near-infrared spectroscopy(fNIRS).Methods:Twenty-eight individu-als with childhood trauma comprised the trauma group,while 32 without trauma formed the control group.The Childhood Trauma Questionnaire(CTQ)assessed abuse and neglect,the Ruminative Responses Scale(RRS)meas-ured repetitive thinking about negative events,and the Iowa Gambling Task(IGT)evaluated decision-making tend-encies.fNIRS data collected during the IGT were used to calculate degree centrality(DC),betweenness centrality(BC),and local efficiency(LE)in prefrontal networks.Mediation analysis explored relationships among childhood trauma,brain function(DC,BC,LE),and ruminative thinking.Results:Compared to controls,the trauma group had decreased DC in bilateral dorsolateral prefrontal cortices,increased DC,BC,and LE in the right inferior frontal gy-rus,and elevated LE in the bilateral frontal poles.BC and LE in the right inferior frontal gyrus partially mediated the relationship between CTQ sexual abuse and RRS scores(48.57％and 41.43％,respectively).Conclusion:Child-hood trauma is significantly associated with changes in prefrontal network properties in early adulthood.Sexual a-buse,in particular,may influence emotional regulation and cognitive functions by altering the network attributes of the right inferior frontal gyrus.

Objective·To investigate the expression of serpin family E member 1(SERPINE1)in gastric cancer and its potential mechanisms in promoting gastric cancer.Methods·Pan-cancer analysis of SERPINE1 was performed by using the TIMER2.0 online website,and the differences in the expression of SERPINE1 in samples with different tumor stages of gastric cancer were analysed by the clinical data of gastric cancer from The Cancer Genome Atlas(TCGA)database.Survival curves were plotted.Quantitative real-time PCR(qRT-PCR)was used to detect mRNA expression in paired samples of clinical gastric cancer tissues.The small interfering RNA(siRNA)transfection technique was used to knock down the expression of SERPINE1 in MGC-803 and SGC-7901 gastric cancer cell lines,and the migration and invasive abilities of gastric cancer cells were investigated by Transwell and invasion chamber experiments.The effects of SERPINE1 knockdown on the angiogenesis of gastric cancer cells were further explored by the migration assay of human umbilical vein endothelial cells(HUVEC)and tubule formation assay of HUVECs.The Gene Expression Omnibus(GEO)dataset was used for differential gene analysis in high and low expression groups based on the median value of SERPINE1 expression.The differentially expressed genes were further analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and Gene Set Enrichment Analysis(GSEA).qRT-PCR was performed to verify the expression levels of key genes related to epithelial-mesenchymal transition(EMT)and angiogenesis.Results·Bioinformatics analysis showed that SERPINE1 was highly overexpressed in a variety of primary tumour tissues,including gastric cancer.SERPINE1 gene expression increased with increasing tumour stage(P<0.001),and increased expression of SERPINE1 was associated with poor prognosis of gastric cancer(P<0.001).qRT-PCR results showed that SERPINE1 was significantly highly expressed in gastric cancer tissues(P=0.038).After knocking down SERPINE1,gastric cancer cell lines MGC-803 and SGC-7901 cells had decreased migration and invasion(P<0.05).Gastric cancer culture supernatants from the SERPINE1-knockdown gastric cancer cell line reduced angiogenesis in HUVECs(P<0.05).Differential genes in gastric cancer patients in the SERPINE1 high-expression group in the GEO database were enriched in cancer-related pathways such as focal adhesion,extracellular matrix receptor interaction,and angiogenesis-related pathways like angiogenesis and the vascular endothelial growth factor(VEGF)signalling pathway.The expression of SERPINE1 was negatively correlated with cadherin 1(CDH1),and positively correlated with other key genes related to EMT and angiogenesis.Moreover,the expression levels of key genes related to EMT and angiogenesis detected by qRT-PCR in SERPINE1 knockdown gastric cancer cell lines(P<0.05),were consistent with the correlation analysis results mentioned above.Conclusion·SERPINE1 expression is elevated in gastric cancer tissues,which could regulate the expression levels of key genes related to EMT and angiogenesis to promote the migration,invasion and angiogenesis of gastric cancer cells.

Objective To explore the oral health management dilemmas of chronic periodontitis patients with implant dentures,so as to provide a reference for formulating scientific and effective oral nursing intervention programs.Methods Based on the information-motivation-behavioral skills model(IMB),the interview outline was formulated.Using the purposive sampling method,patients with chronic periodontitis who underwent implant restoration in a tertiary A stomatological hospital in Taiyuan City,Shanxi Province from April to June 2024 were selected for semi-structured interviews.The data were analyzed by means of directed content analysis.Results A total of 3 core themes were extracted,covering 10 sub-themes,namely knowledge deficiency and information dilemma(lack of oral health-related knowledge,cognitive misunderstanding and memory deviation,difficulty in identifying miscellaneous information),coexistence of emphasis and avoidance(perceived benefits of oral health management,positive feedback reinforcing internal motivation,avoidance induced by psychological burden,the duality of diverse social networks),behavioral skills transformation difficulties(difficulties in home maintenance practice,insufficient professional guidance and support,and uneven self-efficacy).Conclusion The oral health management behavior of chronic periodontitis patients with implant dentures is affected by many factors.We should aim to develop innovative oral health services based on Internet,bridge the cognitive misunderstanding and memory bias of patients,stimulate the internal driving machine of oral health behavior,strengthen the external support of multiple social networks,refine the teaching model of oral health management,and empower oral health self-management.

Objective:To explore the association between childhood trauma and prefrontal cortex functional networks in early adulthood using functional near-infrared spectroscopy(fNIRS).Methods:Twenty-eight individu-als with childhood trauma comprised the trauma group,while 32 without trauma formed the control group.The Childhood Trauma Questionnaire(CTQ)assessed abuse and neglect,the Ruminative Responses Scale(RRS)meas-ured repetitive thinking about negative events,and the Iowa Gambling Task(IGT)evaluated decision-making tend-encies.fNIRS data collected during the IGT were used to calculate degree centrality(DC),betweenness centrality(BC),and local efficiency(LE)in prefrontal networks.Mediation analysis explored relationships among childhood trauma,brain function(DC,BC,LE),and ruminative thinking.Results:Compared to controls,the trauma group had decreased DC in bilateral dorsolateral prefrontal cortices,increased DC,BC,and LE in the right inferior frontal gy-rus,and elevated LE in the bilateral frontal poles.BC and LE in the right inferior frontal gyrus partially mediated the relationship between CTQ sexual abuse and RRS scores(48.57％and 41.43％,respectively).Conclusion:Child-hood trauma is significantly associated with changes in prefrontal network properties in early adulthood.Sexual a-buse,in particular,may influence emotional regulation and cognitive functions by altering the network attributes of the right inferior frontal gyrus.

Objective·To investigate the expression of serpin family E member 1(SERPINE1)in gastric cancer and its potential mechanisms in promoting gastric cancer.Methods·Pan-cancer analysis of SERPINE1 was performed by using the TIMER2.0 online website,and the differences in the expression of SERPINE1 in samples with different tumor stages of gastric cancer were analysed by the clinical data of gastric cancer from The Cancer Genome Atlas(TCGA)database.Survival curves were plotted.Quantitative real-time PCR(qRT-PCR)was used to detect mRNA expression in paired samples of clinical gastric cancer tissues.The small interfering RNA(siRNA)transfection technique was used to knock down the expression of SERPINE1 in MGC-803 and SGC-7901 gastric cancer cell lines,and the migration and invasive abilities of gastric cancer cells were investigated by Transwell and invasion chamber experiments.The effects of SERPINE1 knockdown on the angiogenesis of gastric cancer cells were further explored by the migration assay of human umbilical vein endothelial cells(HUVEC)and tubule formation assay of HUVECs.The Gene Expression Omnibus(GEO)dataset was used for differential gene analysis in high and low expression groups based on the median value of SERPINE1 expression.The differentially expressed genes were further analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and Gene Set Enrichment Analysis(GSEA).qRT-PCR was performed to verify the expression levels of key genes related to epithelial-mesenchymal transition(EMT)and angiogenesis.Results·Bioinformatics analysis showed that SERPINE1 was highly overexpressed in a variety of primary tumour tissues,including gastric cancer.SERPINE1 gene expression increased with increasing tumour stage(P<0.001),and increased expression of SERPINE1 was associated with poor prognosis of gastric cancer(P<0.001).qRT-PCR results showed that SERPINE1 was significantly highly expressed in gastric cancer tissues(P=0.038).After knocking down SERPINE1,gastric cancer cell lines MGC-803 and SGC-7901 cells had decreased migration and invasion(P<0.05).Gastric cancer culture supernatants from the SERPINE1-knockdown gastric cancer cell line reduced angiogenesis in HUVECs(P<0.05).Differential genes in gastric cancer patients in the SERPINE1 high-expression group in the GEO database were enriched in cancer-related pathways such as focal adhesion,extracellular matrix receptor interaction,and angiogenesis-related pathways like angiogenesis and the vascular endothelial growth factor(VEGF)signalling pathway.The expression of SERPINE1 was negatively correlated with cadherin 1(CDH1),and positively correlated with other key genes related to EMT and angiogenesis.Moreover,the expression levels of key genes related to EMT and angiogenesis detected by qRT-PCR in SERPINE1 knockdown gastric cancer cell lines(P<0.05),were consistent with the correlation analysis results mentioned above.Conclusion·SERPINE1 expression is elevated in gastric cancer tissues,which could regulate the expression levels of key genes related to EMT and angiogenesis to promote the migration,invasion and angiogenesis of gastric cancer cells.

Objective To explore the oral health management dilemmas of chronic periodontitis patients with implant dentures,so as to provide a reference for formulating scientific and effective oral nursing intervention programs.Methods Based on the information-motivation-behavioral skills model(IMB),the interview outline was formulated.Using the purposive sampling method,patients with chronic periodontitis who underwent implant restoration in a tertiary A stomatological hospital in Taiyuan City,Shanxi Province from April to June 2024 were selected for semi-structured interviews.The data were analyzed by means of directed content analysis.Results A total of 3 core themes were extracted,covering 10 sub-themes,namely knowledge deficiency and information dilemma(lack of oral health-related knowledge,cognitive misunderstanding and memory deviation,difficulty in identifying miscellaneous information),coexistence of emphasis and avoidance(perceived benefits of oral health management,positive feedback reinforcing internal motivation,avoidance induced by psychological burden,the duality of diverse social networks),behavioral skills transformation difficulties(difficulties in home maintenance practice,insufficient professional guidance and support,and uneven self-efficacy).Conclusion The oral health management behavior of chronic periodontitis patients with implant dentures is affected by many factors.We should aim to develop innovative oral health services based on Internet,bridge the cognitive misunderstanding and memory bias of patients,stimulate the internal driving machine of oral health behavior,strengthen the external support of multiple social networks,refine the teaching model of oral health management,and empower oral health self-management.

Objective To observe the changes in functional connectivity(FC)of raphe nucleus in patients with first-episode depression complicated with suicidal ideation(SI).Methods Ninety-eight first-episode depression patients were prospectively enrolled and assigned into SI group(n=56)or non SI group(n=42)based on complicated with SI or not,while 47 healthy volunteers were recruited as control group.Resting-state functional MRI was performed.FC between dorsal raphe nucleus(DRN),median raphe nucleus(MRN)and the whole brain were analyzed and compared among 3 groups and between each 2 groups,and the correlations of FC of different brain regions with clinical data of SI group were explored.Results Compared with control group,FC between DRN and left cerebellum and left putamen in SI group and non SI group decreased(all P＜0.05),between MRN and right inferior temporal gyrus increased but between MRN and left inferior frontal gyrus,right superior occipital gyrus,left inferior parietal lobule,left putamen decreased(all P＜0.05).FC between DRN and left putamen in SI group was higher than that in non SI group(P＜0.05).FC between MRN and right central posterior gyrus of SI group increased compared with that in the rest 2 groups(both P＜0.05).FC between MRN and left putamen in SI group was positively correlated with body mass score of Hamilton depression scale-24(HAMD-24)(rs=0.297,P=0.026).Conclusion Abnormal changes of FC between raphe nucleus and cortex,also between raphe nucleus and subcortical area occurred,and FC between MRN and left putamen positively correlated with body mass score of HAMD-24 in patients with first-episode depression complicated with SI.