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.

A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.

Objective:To investigate the dynamic changes of serum long non-coding ribonucleic acid antisense non-coding RNA in the INK4 locus (LncRNA ANRIL), long non-coding ribonucleic acid maternally expressed gene 3 (LncRNA MEG3) and inflammatory factors [interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-18 (IL-18) and interleukin-1β (IL-1β)] in patients with acute ischemic stroke and their correlation with neurological impairment.Methods:This prospective study included fifty-two patients with acute ischemic stroke admitted to the Central Hospital of Dalian University of Technology were included, and the neurological impairments of the patients were scored using the National Institutes of Health stroke scale (NIHSS) on the first day of the onset of the disease, and serum LncRNA ANRIL, LncRNA MEG3 and inflammatory factors (IFN-γ, IL-6, IL-18 and IL-1β) were detected using enzyme-linked immunosorbent assay (ELISA) at the first, second and seventh day of the onset of the disease. The correlation between serum LncRNA ANRIL, LncRNA MEG3 and inflammatory factor levels and neurological impairment at each time point was analyzed by Spearman correlation analysis.Results:Among 52 patients, mild group had 22 cases (NIHSS score <5 scores), and moderate-to-severe group had 30 cases (NIHSS score ≥5 scores). In acute ischemic stroke patients with moderate-to-severe group, the expression level of LncRNA MEG3 was higher than in the mild group, but the intergroup difference did not reach statistical significance ( P>0.05). LncRNA ANRIL, LncRNA MEG3, IFN-γ, IL-18 and IL-1β peaked at the same time point in acute ischemic stroke patients, all within second day of the onset of the disease. Spearman correlation analysis showed that the serum LncRNA MEG3 level on the first day of the onset of the disease was significantly positively correlated with NIHSS score ( P = 0.006), and serum LncRNA ANRIL level on seventh day was significantly positively correlated with NIHSS score ( P = 0.049). Conclusions:Serum LncRNA ANRIL, LncRNA MEG3 and inflammatory factors (IL-18, IL-1β and IFN-γ) are highly expressed in patients with acute ischemic stroke, peaking on the second day of onset. LncRNA MEG3 levels on the first day of onset and LncRNA ANRIL levels on the seventh day of onset are helpful in determining the degree of neurological impairment in patients with acute ischemic stroke.

Objective:To investigate the dynamic changes of serum long non-coding ribonucleic acid antisense non-coding RNA in the INK4 locus (LncRNA ANRIL), long non-coding ribonucleic acid maternally expressed gene 3 (LncRNA MEG3) and inflammatory factors [interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-18 (IL-18) and interleukin-1β (IL-1β)] in patients with acute ischemic stroke and their correlation with neurological impairment.Methods:This prospective study included fifty-two patients with acute ischemic stroke admitted to the Central Hospital of Dalian University of Technology were included, and the neurological impairments of the patients were scored using the National Institutes of Health stroke scale (NIHSS) on the first day of the onset of the disease, and serum LncRNA ANRIL, LncRNA MEG3 and inflammatory factors (IFN-γ, IL-6, IL-18 and IL-1β) were detected using enzyme-linked immunosorbent assay (ELISA) at the first, second and seventh day of the onset of the disease. The correlation between serum LncRNA ANRIL, LncRNA MEG3 and inflammatory factor levels and neurological impairment at each time point was analyzed by Spearman correlation analysis.Results:Among 52 patients, mild group had 22 cases (NIHSS score <5 scores), and moderate-to-severe group had 30 cases (NIHSS score ≥5 scores). In acute ischemic stroke patients with moderate-to-severe group, the expression level of LncRNA MEG3 was higher than in the mild group, but the intergroup difference did not reach statistical significance ( P>0.05). LncRNA ANRIL, LncRNA MEG3, IFN-γ, IL-18 and IL-1β peaked at the same time point in acute ischemic stroke patients, all within second day of the onset of the disease. Spearman correlation analysis showed that the serum LncRNA MEG3 level on the first day of the onset of the disease was significantly positively correlated with NIHSS score ( P = 0.006), and serum LncRNA ANRIL level on seventh day was significantly positively correlated with NIHSS score ( P = 0.049). Conclusions:Serum LncRNA ANRIL, LncRNA MEG3 and inflammatory factors (IL-18, IL-1β and IFN-γ) are highly expressed in patients with acute ischemic stroke, peaking on the second day of onset. LncRNA MEG3 levels on the first day of onset and LncRNA ANRIL levels on the seventh day of onset are helpful in determining the degree of neurological impairment in patients with acute ischemic stroke.

Objective:To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) .Methods:A retrospective analysis was conducted on the clinical and pathological data of 34 newly diagnosed PTL patients admitted to Beijing Tongren Hospital from September 2010 to February 2023. The Kaplan-Meier survival curve and Log-rank test were used for survival analysis, and the Cox regression model was applied for univariate analysis of prognostic factors.Results:All 34 PTL patients presented with cervical mass as the initial clinical manifestation. There were 9 males and 25 females. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) in 29 patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 5 patients. Among the DLBCL patients, 6 had B symptoms, 17 had an Eastern Cooperative Oncology Group (ECOG) score of ≥2, the Ann Arbor staging was stage Ⅰ-Ⅱ in 21 cases and stage Ⅲ-Ⅳ in 8 cases, the tumor diameter was ≥10 cm in 4 cases, and 14 had concurrent Hashimoto thyroiditis; 27 cases received chemotherapy, with 21 cases achieving complete remission (CR), 2 cases partial remission (PR), and 6 cases of disease progression; the 5-year progression-free survival and overall survival rates were 78.9% and 77.4%, respectively; univariate survival analysis showed that B symptoms, tumor diameter ≥10 cm, and Ann Arbor stage Ⅲ-Ⅳ were significant factors affecting patient prognosis ( P<0.05). MALT lymphoma patients were all in stages Ⅰ-Ⅱ, had an ECOG score of 0-1, and were without B symptoms. All patients underwent surgical resection, with 4 cases achieving CR and 1 case PR. Conclusion:PTL is more common in females with concurrent Hashimoto thyroiditis, with the majority of pathological types being B-cell lymphoma. The main treatment is chemotherapy, supplemented by radiotherapy and surgery, and the prognosis is relatively favorable.

Objective To investigate the clinical effect of apical microsurgery combined with guided bone regeneration(GBR)on refractory apical periodontitis and masticatory function.Methods A total of 82 patients with refractory apical periodontitis admitted to our hospital from June 2019 to September 2021 were selected as the study subjects,and they were divided into the control group and the com-bined group according to the random number table,with 41 cases in each group.The control group was treated with apical microsurgery,and the combined group was treated with apical microsurgery combined with GBR.The clinical efficacy,masticatory function and the levels of bone absorption markers[Wnt3a,osteoprotegerin(OPG),receptor activator of nuclear factor-κB ligand(RANKL)]of patients in the two groups were compared.Results The total effective rate of the combined group(100%)was higher than that of the control group(85.37%),the difference was statistically significant(P<0.05).The masticatory efficiency and bite force of patients in both groups increased gradually 3,6 and 12 months after operation(P<0.05),which were higher in the combined group compared with the control group(P<0.05).The tooth mobility of patients in both groups decreased gradually 3,6 and 12 months after operation,and the tooth mobility of patients 3 and 6 months after operation in the combined group were lower than those in the control group(P<0.05).The levels of Wnt3a and OPG of patients 1 week after operation in both groups increased,which were higher in the combined group compared with the control group(P<0.05).The RANKL level of gingival crevicular fluid of patients 1 week after operation in both groups decreased,and which was lower in the combined group compared with the control group(P<0.05).Conclusion The microapical surgery combined with GBR is effective for refractory apical periodontitis,which can effectively inhibit bone resorption,and improve masticatory function.

Objective To investigate the changes of serum metabolites in patients with occupational chronic lead poisoning using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 14 patients with occupational chronic lead poisoning were selected as the poisoning group, and 14 healthy people without occupational hazard exposure history were selected as the control group using the judgment sampling method. Serum of the individuals from the two groups was collected. Non-targeted metabolomics technology based on ultra high performance liquid chromatography-tandem mass spectrometry was used to detect serum metabolite levels in the two groups. Differential metabolites (DMs) were screened by the principal component analysis, partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis, and related metabolic pathways were explored. Results The blood lead level in the poisoning group was higher than that in the control group (median: 359.59 vs 5.04 μg/L, P<0.01). There were significant differences in serum metabolites between the poisoning group and control group. After the combination of results from the positive and negative ion patterns, a total of 89 DMs were screened in serum of patients in the poisoning group, including 50 upregulated and 39 downregulated metabolites compared with the control group. The serum DMs of poisoning group were mainly enriched in arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism in malignant tumor, glycerophospholipid metabolism and ether lipid metabolism compared with the control group (all P<0.05). Conclusion Abnormal changes of serum metabolic profile occurred in patients with occupational chronic lead poisoning. The metabolic pathways such as arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism, glycerophospholipid metabolism and ether lipid metabolism may be involved in the occurrence and development of lead poisoning.

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 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.