OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans

With the increasing demand for dynamic,real-time and rapid qualitative analysis of chemical composition in areas such as emergency response and space exploration,chip-scale mass spectrometers have attracted significant attention.These devices are expected to drive the integration of mass spectrometry with micro/nano-fabrication and intelligent sensing technologies,fostering profound innovation and breakthroughs in analytical chemistry.As an excellent mass analyzer,the ion trap exhibits numerous advantages,and its miniaturization creates favorable conditions for the high-density integration of miniature mass spectrometers.However,the reduction in ion storage capacity may compromise its sensitivity and dynamic range,rendering the study of ion unidirectional ejection in highly miniaturized ion traps of significant practical importance.In this work,a research was conducted on achieving efficient ion unidirectional ejection while maintaining high mass resolution in the extremely miniature hyperbolic linear ion trap(M-HLIT)with a field radius of 1 mm,and an electric field compensation method was proposed,which combined asymmetric electrode stretching and unbalanced RF voltage to achieve high-precision optimization of the electric field composition.Simulations showed that in an ideal structure,this method achieved 100％unidirectional ejection efficiency with the mass resolution of 518,significantly outperforming traditional asymmetric structure method(365)and unbalanced voltage method(321).Following the introduction of ion ejection slots,further optimization through bidirectional stretching and electrical parameters improved the resolution to 790 while maintaining a unidirectional ejection efficiency of 93％.This method eliminated the requirement for additional excitation voltage,offering an ideal solution for the miniature mass analyzer with high detection performance of chip-level mass spectrometers.

Objective:To explore the role of cytokines and glucocorticoid receptors (GR) in adolescent depression and childhood trauma.Methods:Using convenient sampling,80 adolescents with depression were recruited from the in-patient department of the Mental Health Center,First Hospital of Hebei Medical University from August 2021 to December 2022. Meanwhile,70 healthy adolescents were recruited to participate in the study. Life and learning stress,childhood trauma,anxiety and depression symptoms were evaluated using adolescent Life Events Scale,Childhood Trauma Questionnaire,Hamilton Depression Scale-17 (HAMD 17) and Hamilton Anxiety Scale(HAMA). Serum glucocorticoid receptor and plasma 12 cytokines were also detected. SPSS 25.0 and AMOS 26.0 was used for statistical analysis. The rank sum test or Chi-square test was used to compare the demographic data and blood indicators between adolescents with and without depression. Spearman method was used to examine the correlation between childhood trauma,GR,cytokines and depression. Maximum likelihood estimation method was performed to test the mediating effect,and the average path coefficient was obtained after testing the indirect path by Bootstrap method. If the 95% confidence interval ( CI) does not contain 0,the intermediary effect is significant. Results:There was significant difference in GR concentration between adolescents with and without depression ( Z=-10.50, P<0.001). IL-1β,IL-2,IL-5,IL-10,IL-12,IL-17 and IFN-α were also significantly different between the two groups. Spearman correlation analysis showed that HAMD 17 and HAMA scores were associated with emotional abuse,emotional neglect,physical abuse,CTQ total score and cytokine level IL-5,IFN-α were positively correlated. Physical neglect and IL-1β were only positively correlated with HAMD 17 score. GR was negatively associated with emotional abuse ( r=-0.523, P<0.001),emotional neglect ( r=-0.245, P=0.002),sexual abuse ( r=-0.172, P=0.035),physical abuse score ( r=-0.180, P=0.027),CTQ total score ( r=-0.562, P<0.001),HAMD 17 score ( r=-0.783--0.271, P<0.001),HAMA score( r=-0.741--0.602, P<0.001),IL-1β ( r=-0.217, P=0.008),IL-5 ( r=-0.334, P<0.001),and IFN-α ( r=-0.276, P=0.001). IL-5 level was positively correlated with emotional abuse score ( r=0.211, P=0.009) and CTQ total score ( r=0.201, P=0.014). IFN-α level was positively correlated with emotional abuse score ( r=0.207, P=0.011) and CTQ total score ( r=0.166, P=0.042). The mediating effect showed that GR played a partial mediating role between childhood trauma and depression (indirect effect: effect size 0.294, S.E. 0.043,95 %CI=0.236-0.398). GR and cytokine IL-5 play a chain mediating role between childhood trauma and depression (indirect effect: effect size 0.067, S.E. 0.040,95 %CI=0.023-0.147). Conclusion:GR,and cytokine IL-5 play a mediating role between adolescent depression and childhood trauma.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To observe the changes in the nutritional status of pediatric patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT)for one year,and to analyze the risk factors.Methods:We collected data from 88 pediatric patients who underwent allo-HSCT at the Department of Hematology and Oncology in Children's Hospital of Nanjing Medical University between May 2018 and November 2022.All pediatric patients underwent nutritional status analysis before transplantation,at enrollment,3 months,6 months and 1 year after allo-HSCT.Linear regression model was used to analyze the risk factors for growth rate.Results:The body mass index Z score(BMI-Z)before allo-HSCT was(0.096±1.349),and decreased to(-0.258±1.438)、(-0.715±1.432)、(-0.584±1.444)at enrollment,3 months,6 months after allo-HSCT,and(-0.130±1.317)at 1 year after allo-HSCT(P<0.001).There was no significant change in BMI-Z between pre-transplantation and 1 year after transplantation(P=1.000).Height for age Z score(HAZ)before transplantation was(0.137±1.305)and decreased to(-0.083±1.267)、(-0.221±1.299)、(-0.269±1.282)in 3 months,6 months and 1 year after allo-HSCT(P<0.001).Multivariate linear regression showed that age≥10 years old(P=0.015)and chronic graft-versus-host disease(cGVHD)(P=0.005)were independent risk factors for change in HAZ.Conclusion:The BMI-Z of pediatric patients treated with allo-HSCT returned to the pre-transplantation level after one year,while HAZ continued to decrease.Allo-HSCT may cause impaired growth rate in pediatric patients.Attention should be paid to HAZ changes in pediatric patients before and after allo-HSCT,especially in pediatric patients≥10 years old of age and those with cGVHD.Effective nutritional intervention should be provided in time.

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.

Objective:To explore the role of cytokines and glucocorticoid receptors (GR) in adolescent depression and childhood trauma.Methods:Using convenient sampling,80 adolescents with depression were recruited from the in-patient department of the Mental Health Center,First Hospital of Hebei Medical University from August 2021 to December 2022. Meanwhile,70 healthy adolescents were recruited to participate in the study. Life and learning stress,childhood trauma,anxiety and depression symptoms were evaluated using adolescent Life Events Scale,Childhood Trauma Questionnaire,Hamilton Depression Scale-17 (HAMD 17) and Hamilton Anxiety Scale(HAMA). Serum glucocorticoid receptor and plasma 12 cytokines were also detected. SPSS 25.0 and AMOS 26.0 was used for statistical analysis. The rank sum test or Chi-square test was used to compare the demographic data and blood indicators between adolescents with and without depression. Spearman method was used to examine the correlation between childhood trauma,GR,cytokines and depression. Maximum likelihood estimation method was performed to test the mediating effect,and the average path coefficient was obtained after testing the indirect path by Bootstrap method. If the 95% confidence interval ( CI) does not contain 0,the intermediary effect is significant. Results:There was significant difference in GR concentration between adolescents with and without depression ( Z=-10.50, P<0.001). IL-1β,IL-2,IL-5,IL-10,IL-12,IL-17 and IFN-α were also significantly different between the two groups. Spearman correlation analysis showed that HAMD 17 and HAMA scores were associated with emotional abuse,emotional neglect,physical abuse,CTQ total score and cytokine level IL-5,IFN-α were positively correlated. Physical neglect and IL-1β were only positively correlated with HAMD 17 score. GR was negatively associated with emotional abuse ( r=-0.523, P<0.001),emotional neglect ( r=-0.245, P=0.002),sexual abuse ( r=-0.172, P=0.035),physical abuse score ( r=-0.180, P=0.027),CTQ total score ( r=-0.562, P<0.001),HAMD 17 score ( r=-0.783--0.271, P<0.001),HAMA score( r=-0.741--0.602, P<0.001),IL-1β ( r=-0.217, P=0.008),IL-5 ( r=-0.334, P<0.001),and IFN-α ( r=-0.276, P=0.001). IL-5 level was positively correlated with emotional abuse score ( r=0.211, P=0.009) and CTQ total score ( r=0.201, P=0.014). IFN-α level was positively correlated with emotional abuse score ( r=0.207, P=0.011) and CTQ total score ( r=0.166, P=0.042). The mediating effect showed that GR played a partial mediating role between childhood trauma and depression (indirect effect: effect size 0.294, S.E. 0.043,95 %CI=0.236-0.398). GR and cytokine IL-5 play a chain mediating role between childhood trauma and depression (indirect effect: effect size 0.067, S.E. 0.040,95 %CI=0.023-0.147). Conclusion:GR,and cytokine IL-5 play a mediating role between adolescent depression and childhood trauma.

Objective:This study aimed to investigate the influence of FGFR3 gene mutations on the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma (NDMM) .Methods:A total of 198 patients with NDMM admitted to the Department of Hematology in Jiangsu Province Hospital between January 2016 and February 2023 were retrospectively analyzed. Next-generation sequencing and cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization were performed for all patients. The prognostic significance of FGFR3 mutation and clinical features were analyzed using the Log-rank test and Cox proportional hazards model.Results:Among 198 patients, 28 carried the FGFR3 gene mutation. These patients had significantly lower serum albumin levels, higher β 2-microglobulin levels, advanced Revised International Staging System stages, more frequent occurrence of t (4;14) , and shorter median progression-free survival (PFS) time (28 months vs 33 months, P=0.024) and overall survival (OS) time (54 months vs undefined, P=0.028) than patients without FGFR3 mutation. Additionally, patients carrying either FGFR3 mutation or t (4;14) had lower PFS (30 months vs 38 months, P=0.012) and OS (54 months vs undefined, P=0.017) than those without. The Cox proportional hazards model identified FGFR3 mutation as an independent risk factor for PFS and OS. Conclusion:FGFR3 gene mutation was an unfavorable independent prognostic predictor for NDMM.

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic bio-markers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the"masking"effect caused by high-abundance proteins.The relative abundance of middle-and low-abundance proteins increased substantially from 2.54％to 54.41％,and the top 20 high-abundance proteins decreased from 83.63％to 25.77％.Notably,our method can quantify approxi-mately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins iden-tified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.