Aim To study the mechanism of adipose mesenchymal stem cell exosomes(ASC-exo)inhibition of fluorescein isothiocyanate(FITC)-induced atopic dermatitis(AD).Methods The mouse age,extrac-tion method,and the concentration of a solution of typeⅠ collagen enzyme and other conditions were compared to study the effects on the morphology and quantity of adipose mesenchymal stem cells(ASCs)after extrac-ted.FITC-induced mouse model in vivo was estab-lished and different doses of ASC-exo were given to measure ear thickness,ear weight and ear scratching times of mice.HE staining was used to observe the pathological changes of ear tissue of mice.The non-toxicity of ASC-exo was detected.IgE,IL-5,IL-13 and other cytokines were detected by ELISA.The gene ex-pressions of TSLP,IL-33,occludin,Claudin-1(CLDN-1)and E-cadherin were detected by RT-qPCR.The protein expression was detected by immunohistochemis-try.Results An efficient method for extracting ASCs was established.Compared with the blank group,mice in the model group showed obvious AD symptoms.Compared with the model group,ASC-exo administra-tion group significantly reduced the number of ear scratches,epidermal thickening,inflammatory cell infil-tration and the secretion of Th2 cytokines IL-5 and IL-13.Meanwhile,ASC-exo administration group signifi-cantly increased the expression of structural proteins CLDN-1 and occludin in epithelial cells and decreased the expression of TSLP and IL-33.Conclusions ASC-exo can significantly improve Th2 skin inflamma-tion in AD mice,and its mechanism may be through in-creasing the expression of tight junction proteins and adhesion link protein in epithelial cells,repairing the skin barrier,and inhibiting the key promoters of allergy TSLP and IL-33.

Objective:To evaluate the association between postoperative delirium (POD) and preoperative frailty in elderly patients undergoing knee or hip arthroplasty.Methods:This nested case-control study utilized medical records from elderly patients who underwent knee or hip arthroplasty under combined spinal-epidural anesthesia at Qingdao Municipal Hospital between September 2021 and May 2023. Participants were divided into 2 groups based on clinically diagnosed POD: POD group ( n=53) and non-POD group ( n=256). Univariate analysis was conducted on suspected influencing factors, and logistic regression analysis was utilized to identify the risk factors for POD. Receiver operating characteristic and clinical decision curves were plotted to evaluate the predictive performance of these risk factors for POD. Mediation analysis was performed, and a clinically applicable nomogram was constructed to achieve visual prediction of outcomes. Results:There were statistically significant differences in age, preoperative frailty, body mass index, American Society of Anesthesiologists Physical Status classification, Memorial Delirium Assessment Scale scores, and concentrations of Aβ 42, Aβ 40, phosphorylated tau protein (p-tau protein) and tau protein, Aβ 42/tau ratio and Aβ 42/p-tau ratio in cerebrospinal fluid (CSF) between non-POD group and POD group ( P<0.05). Preoperative frailty was a risk factor for POD ( P<0.05). Mediation analysis revealed that the association between preoperative frailty and POD was mediated by CSF tau protein concentrations. The area under the receiver operating characteristic curve of preoperative frailty and CSF biomarker concentrations in predicting POD was 0.974 ( P<0.05). The clinical decision curve demonstrated that the model combining the preoperative frailty and CSF biomarker concentrations predicted a higher net benefit ( P<0.05). The clinical decision curve showed that the model combining preoperative frailty and CSF biomarker concentrations predicted a higher net benefit. Conclusions:Preoperative frailty is a risk factor for POD in elderly patients undergoing knee or hip arthroplasty, and its combination with CSF biomarker concentrations can effectively predict the occurrence of POD. CSF tau concentration mediates the association between preoperative frailty and development of POD.

Objective:To evaluate the association between preoperative cardiometabolic multimorbidity (CMM) and postoperative delirium (POD) in elderly patients undergoing knee or hip replacement.Methods:Based on a perioperative neurocognitive dysfunction and biomarker lifestyle cohort, a nested case-control study was conducted using medical records of patients scheduled for elective knee or hip joint replacement at Qingdao Municipal Hospital from January 2022 to November 2023. Patients were divided into POD group ( n=124) and non-POD group ( n=414) based on whether POD occurred. The influencing factors were collected, and intergroup differences were analyzed. Logistic regression was used to identify the risk factors for POD, and sensitivity analysis was conducted to assess the stability of the regression model. A mediation model was employed to examine whether cerebrospinal fluid (CSF) biomarkers mediated the association between CMM and POD. Results:There were statistically significant differences in the rate of CMM, age, years of education, rate of hypertension, rate of diabetes mellitus, rate of coronary heart diseases, rate of stroke, Aβ 42 concentration, t-tau concentration, p-tau concentration, Aβ 42/t-tau ratio, and Aβ 42/p-tau ratio in CSF between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative CMM was a risk factor for POD ( P<0.05). Mediation analysis revealed that the relationship between CMM and POD was partly mediated by Aβ 42 concentrations in CSF. Conclusions:Preoperative CMM is a risk factor for POD in elderly patients undergoing knee or hip replacement, and the CSF Aβ 42 concentration may play a partly mediating role in the association between preoperative CMM and POD.

Objective:To learn about the levels of 25-hydroxy vitamin D (25-OH VD), TBNK lymphocyte subsets, and cytokines in peripheral blood of patients with brucellosis.Methods:A prospective design was adopted, one hundred patients with brucellosis admitted to the Department of Infectious Diseases, Beidahuang Industry Group General Hospital from May 2024 to February 2025 were selected as the brucellosis group, and one hundred healthy individuals who underwent physical examinations at the hospital during the same period were selected as the control group. The peripheral blood 25-OH VD levels were detected by chemiluminescence method. Further, 100 patients with brucellosis were divided into a brucellosis combined with osteoarthritis group (74 cases) and a brucellosis without osteoarthritis group (26 cases). Flow cytometry was used to detect the counts of peripheral blood TBNK lymphocyte subsets and cytokine levels. Meanwhile, Spearman rank correlation was used to analyze the correlation between peripheral blood 25-OH VD levels and TBNK lymphocyte subsets counts as well as cytokine levels in patients with brucellosis complicated by osteoarthritis.Results:The peripheral blood 25-OH VD level in the brucellosis group [20.31 (15.74, 24.35) ng/ml] was significantly lower than that of the control group [25.18 (21.13, 29.59) ng/ml], and the difference was statistically significant ( Z = - 5.07, P < 0.001). The peripheral blood 25-OH VD level [18.05 (13.79, 23.74) vs 22.43 (19.93, 28.25) ng/ml], CD4 + T cell count [(860 ± 275) vs (1 036 ± 376) cells/μl], and interleukin (IL)-6 levels [4.17 (2.14, 9.41) vs 7.83 (5.97, 11.34) ng/L] in the brucellosis combined with osteoarthritis group were significantly lower than those in the brucellosis without osteoarthritis group ( Z/t = - 2.88, 2.20, - 2.85, P = 0.004, 0.035, 0.004). Correlation analysis showed that the peripheral blood 25-OH VD level in patients with brucellosis complicated by osteoarthritis was positively correlated with the counts of CD45 +, CD3 + T, CD4 + T, CD8 + T, and natural killer cells ( r = 0.31, 0.26, 0.25, 0.25, 0.25, P = 0.007, 0.027, 0.032, 0.031, 0.032), and negatively correlated with IL-17A level ( r = - 0.40, P < 0.001). Conclusion:Patients with brucellosis have insufficient 25-OH VD, and those with osteoarthritis have lower 25-OH VD level, CD4 + T cell count, and IL-6 level than those without osteoarthritis.

Objective:To evaluate the association between postoperative delirium (POD) and preoperative frailty in elderly patients undergoing knee or hip arthroplasty.Methods:This nested case-control study utilized medical records from elderly patients who underwent knee or hip arthroplasty under combined spinal-epidural anesthesia at Qingdao Municipal Hospital between September 2021 and May 2023. Participants were divided into 2 groups based on clinically diagnosed POD: POD group ( n=53) and non-POD group ( n=256). Univariate analysis was conducted on suspected influencing factors, and logistic regression analysis was utilized to identify the risk factors for POD. Receiver operating characteristic and clinical decision curves were plotted to evaluate the predictive performance of these risk factors for POD. Mediation analysis was performed, and a clinically applicable nomogram was constructed to achieve visual prediction of outcomes. Results:There were statistically significant differences in age, preoperative frailty, body mass index, American Society of Anesthesiologists Physical Status classification, Memorial Delirium Assessment Scale scores, and concentrations of Aβ 42, Aβ 40, phosphorylated tau protein (p-tau protein) and tau protein, Aβ 42/tau ratio and Aβ 42/p-tau ratio in cerebrospinal fluid (CSF) between non-POD group and POD group ( P<0.05). Preoperative frailty was a risk factor for POD ( P<0.05). Mediation analysis revealed that the association between preoperative frailty and POD was mediated by CSF tau protein concentrations. The area under the receiver operating characteristic curve of preoperative frailty and CSF biomarker concentrations in predicting POD was 0.974 ( P<0.05). The clinical decision curve demonstrated that the model combining the preoperative frailty and CSF biomarker concentrations predicted a higher net benefit ( P<0.05). The clinical decision curve showed that the model combining preoperative frailty and CSF biomarker concentrations predicted a higher net benefit. Conclusions:Preoperative frailty is a risk factor for POD in elderly patients undergoing knee or hip arthroplasty, and its combination with CSF biomarker concentrations can effectively predict the occurrence of POD. CSF tau concentration mediates the association between preoperative frailty and development of POD.

Objective:To evaluate the association between preoperative cardiometabolic multimorbidity (CMM) and postoperative delirium (POD) in elderly patients undergoing knee or hip replacement.Methods:Based on a perioperative neurocognitive dysfunction and biomarker lifestyle cohort, a nested case-control study was conducted using medical records of patients scheduled for elective knee or hip joint replacement at Qingdao Municipal Hospital from January 2022 to November 2023. Patients were divided into POD group ( n=124) and non-POD group ( n=414) based on whether POD occurred. The influencing factors were collected, and intergroup differences were analyzed. Logistic regression was used to identify the risk factors for POD, and sensitivity analysis was conducted to assess the stability of the regression model. A mediation model was employed to examine whether cerebrospinal fluid (CSF) biomarkers mediated the association between CMM and POD. Results:There were statistically significant differences in the rate of CMM, age, years of education, rate of hypertension, rate of diabetes mellitus, rate of coronary heart diseases, rate of stroke, Aβ 42 concentration, t-tau concentration, p-tau concentration, Aβ 42/t-tau ratio, and Aβ 42/p-tau ratio in CSF between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative CMM was a risk factor for POD ( P<0.05). Mediation analysis revealed that the relationship between CMM and POD was partly mediated by Aβ 42 concentrations in CSF. Conclusions:Preoperative CMM is a risk factor for POD in elderly patients undergoing knee or hip replacement, and the CSF Aβ 42 concentration may play a partly mediating role in the association between preoperative CMM and POD.

Aim To study the mechanism of adipose mesenchymal stem cell exosomes(ASC-exo)inhibition of fluorescein isothiocyanate(FITC)-induced atopic dermatitis(AD).Methods The mouse age,extrac-tion method,and the concentration of a solution of typeⅠ collagen enzyme and other conditions were compared to study the effects on the morphology and quantity of adipose mesenchymal stem cells(ASCs)after extrac-ted.FITC-induced mouse model in vivo was estab-lished and different doses of ASC-exo were given to measure ear thickness,ear weight and ear scratching times of mice.HE staining was used to observe the pathological changes of ear tissue of mice.The non-toxicity of ASC-exo was detected.IgE,IL-5,IL-13 and other cytokines were detected by ELISA.The gene ex-pressions of TSLP,IL-33,occludin,Claudin-1(CLDN-1)and E-cadherin were detected by RT-qPCR.The protein expression was detected by immunohistochemis-try.Results An efficient method for extracting ASCs was established.Compared with the blank group,mice in the model group showed obvious AD symptoms.Compared with the model group,ASC-exo administra-tion group significantly reduced the number of ear scratches,epidermal thickening,inflammatory cell infil-tration and the secretion of Th2 cytokines IL-5 and IL-13.Meanwhile,ASC-exo administration group signifi-cantly increased the expression of structural proteins CLDN-1 and occludin in epithelial cells and decreased the expression of TSLP and IL-33.Conclusions ASC-exo can significantly improve Th2 skin inflamma-tion in AD mice,and its mechanism may be through in-creasing the expression of tight junction proteins and adhesion link protein in epithelial cells,repairing the skin barrier,and inhibiting the key promoters of allergy TSLP and IL-33.

Objective:To learn about the levels of 25-hydroxy vitamin D (25-OH VD), TBNK lymphocyte subsets, and cytokines in peripheral blood of patients with brucellosis.Methods:A prospective design was adopted, one hundred patients with brucellosis admitted to the Department of Infectious Diseases, Beidahuang Industry Group General Hospital from May 2024 to February 2025 were selected as the brucellosis group, and one hundred healthy individuals who underwent physical examinations at the hospital during the same period were selected as the control group. The peripheral blood 25-OH VD levels were detected by chemiluminescence method. Further, 100 patients with brucellosis were divided into a brucellosis combined with osteoarthritis group (74 cases) and a brucellosis without osteoarthritis group (26 cases). Flow cytometry was used to detect the counts of peripheral blood TBNK lymphocyte subsets and cytokine levels. Meanwhile, Spearman rank correlation was used to analyze the correlation between peripheral blood 25-OH VD levels and TBNK lymphocyte subsets counts as well as cytokine levels in patients with brucellosis complicated by osteoarthritis.Results:The peripheral blood 25-OH VD level in the brucellosis group [20.31 (15.74, 24.35) ng/ml] was significantly lower than that of the control group [25.18 (21.13, 29.59) ng/ml], and the difference was statistically significant ( Z = - 5.07, P < 0.001). The peripheral blood 25-OH VD level [18.05 (13.79, 23.74) vs 22.43 (19.93, 28.25) ng/ml], CD4 + T cell count [(860 ± 275) vs (1 036 ± 376) cells/μl], and interleukin (IL)-6 levels [4.17 (2.14, 9.41) vs 7.83 (5.97, 11.34) ng/L] in the brucellosis combined with osteoarthritis group were significantly lower than those in the brucellosis without osteoarthritis group ( Z/t = - 2.88, 2.20, - 2.85, P = 0.004, 0.035, 0.004). Correlation analysis showed that the peripheral blood 25-OH VD level in patients with brucellosis complicated by osteoarthritis was positively correlated with the counts of CD45 +, CD3 + T, CD4 + T, CD8 + T, and natural killer cells ( r = 0.31, 0.26, 0.25, 0.25, 0.25, P = 0.007, 0.027, 0.032, 0.031, 0.032), and negatively correlated with IL-17A level ( r = - 0.40, P < 0.001). Conclusion:Patients with brucellosis have insufficient 25-OH VD, and those with osteoarthritis have lower 25-OH VD level, CD4 + T cell count, and IL-6 level than those without osteoarthritis.

Objective To evaluate the bioequivalency of single administration of metformin hydrochloride sustained-release tablets(Ⅲ)and double administration of metformin hydrochloride tablet by self-cross test in healthy subjects.Methods A two-cycle,open,self-controlled cross-control trial was conducted in which 10 cases healthy subjects first received test prepatration metformin hydrochloride sustained-release tablet(Ⅲ)2.0 g and then received reference preparation(metformin hydrochloride tablet)1.0 g twice daily after a 7-day washout period.The plasma concentrations of metformin at different time points after administration were measured by liquid chromatography tandem mass spectrometry(LC-MS/MS).The pharmacokinetic parameters were calculated by Analyst 1.6.3,and the bioequivalency of the two drugs was evaluated.A double unilateral t-test and 90％confidence interval were used to assess the equivalence.A non-parametric test statistical analysis was used to evaluate the equivalence of the secondary parameter tmax.Results The pharmacokinetic parameters of test prepatration and reference preparation were AUC0-24h were(16.43±4.46)and(18.69±4.68)μg·h·mL-1,AUCINF-obs were(17.60±4.56)and(20.09±5.78)μg·h·mL-1,Cmax were(1 893.97±585.88)and(1 437.35±281.21)ng·mL-1,tmax were(7.60±1.58)and(4.70±2.41)h;t1/2 were(10.95±2.58)and(3.33±0.62)h.Conclusion The peak time and half-life of metformin hydrochloride sustained-release tablet(Ⅲ)after single administration in Chinese healthy subjects are longer than that of metformin hydrochloride tablet,and the bioequivalency is comparable to that of metformin hydrochloride tablet after two administration.