Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P＜0.05,P＜0.01),and the high-dose EPL group reduced the serum RF in mice(P＜0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P＞0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P＜0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P＜0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P＜0.01).EPL significantly increased the pro-tein expression of Bcl-2(P＜0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P＜0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.

Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P＜0.05,P＜0.01),and the high-dose EPL group reduced the serum RF in mice(P＜0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P＞0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P＜0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P＜0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P＜0.01).EPL significantly increased the pro-tein expression of Bcl-2(P＜0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P＜0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.

Refractory prolactinoma is the most common pituitary neuroendocrine tumor.Dopamine receptor agonists(DA)are the primary choice for drug treatment.Most patients with prolactinomas respond well to DA.However,a minority of prolactinomas patients still show resistance to DA.Although drug-resistant and refractory prolactinomas are rare in clinical practice,their treatment is extremely challenging.Even a combination of drug therapy,multiple surgeries,and radiotherapy may not yield satisfactory outcomes.Therefore,standardizing the diagnosis and treatment process and pathway for refractory prolactionmas and exploring more effective multidisciplinary collaborative treatment strategies are urgent problems to be solved.In the clinical management of refractory prolactinomas,it is often necessary to consider the patient's condition comprehensively,replace other types of DA,or consider surgery,radiotherapy,and immunotherapy,which requires multidisciplinary diagnosis and treatment.This review synthesizes the latest literature at home and abroad to systematically discuss the latest advances in drug therapy,surgery,and radiotherapy treatments for refractory prolactionmas,aiming to provide new ideas for basic research,clinical diagnosis and treatment.

Objective To compare the effects of different dose prediction models of sufentanil in elderly hip arthroplasty with ultrasound-guided bow tie fascia iliac block.Methods A total of 90 elderly patients who underwent ultrasound-guided bow tie fascia iliac during hip arthroplasty in our hospital from June 2018 to June 2022 were selected.The dose of sufentanil was determined by a linear regression(ALR),multiple linear regression(MLR)or deep belief networks(DBN).Patients were randomly divided into the ALR group,the MLR group and the DBN group,with 30 cases in each group.The analgesic effect,hemodynamic index,inflammatory factor level and surgical index were compared among all groups.Kaplan-Meier method was used to analyze the incidence of hip infection 2 weeks after surgery in each group.Results There was no significant difference in the gender,age,body weight,American Society of Anesthesiologists(ASA)classification or complications among all groups(P>0.05).The Harris score 24 hours after surgery and duration of sensory block in the DBN group were higher/longer than those in the ALR group,numerical rating scale(NRS)score 24 hours after surgery,mean arterial pressure(MAP)and heart rate(HR)at the beginning of surgery and 30 minutes after surgery,levels of interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)24 hours after surgery,onset time of sensory block,and number of patient controlled analgesia(PCA)compression were lower/earlier/less than those in the ALR group,the modified observer's assessment of alertness/sedation scale(OAA/S)score 24 hours after surgery was significantly lower than those in the ALR group and the MLR group,with statistically significant differences(P<0.05).Harris score 24 hours after surgery and duration of sensory block in the MLR group were higher/longer than those in the ALR group,modified OAA/S score 12 hours after surgery,MAP 30 minutes after surgery,levels of IL-17 and TNF-α 24 hours after surgery,onset time of sensory block,and the number of PCA compressions were lower/longer/less than those in the ALR group,with statistically significant differences(P<0.05).Kaplan-Meier analysis showed that there were significant differences in the incidences of hip infection 2 weeks after surgery among all groups(P<0.05),and there were significant differences in the incidences of hip infection 2 weeks after surgery between the ALR group and the DBN group(P<0.05).Conclusion The effectiveness of calculating the dose of sufentanil using the MLR and DBN in elderly hip arthroplasty with bow tie fascia iliac block is better than that of ALR,and the advantage of DBN is more obvious.

Objective To analyze the definition of mobile health readiness,and provide a theoretical basis for assessment and clinical practice.Methods Web of Science,PubMed,Embase,Cochrane Library,CINAHL,CNKI,Wanfang data,VIP,and China Biomedical Literature Service System databases were searched.The search time limit was from the establishment of the database to January 2024.Walker and Avant's methods were used to perform concept analysis.Results As a result,38 articles were selected for analysis.Mobile health readiness can be classified into 4 defined attributes:willingness to adopt new technologies,digital health literacy,technological accessibility,and supporting environment and resources.Antecedents can be discussed from the aspects of digital gap,health care service,and user factors.Mobile health readiness can impact on users and health care systems.Conclusion The concept attributes of mobile health readiness were identified by concept analysis method,which provides references for community nurses to assess the mobile health readiness of users.In the future,researchers can combine the connotations of mobile health readiness to develop assessment tools,and construct interventions for the implementation of mobile health,thereby promoting the application of mobile health in China and the development of intelligent nursing.

Objective To analyze the definition of mobile health readiness,and provide a theoretical basis for assessment and clinical practice.Methods Web of Science,PubMed,Embase,Cochrane Library,CINAHL,CNKI,Wanfang data,VIP,and China Biomedical Literature Service System databases were searched.The search time limit was from the establishment of the database to January 2024.Walker and Avant's methods were used to perform concept analysis.Results As a result,38 articles were selected for analysis.Mobile health readiness can be classified into 4 defined attributes:willingness to adopt new technologies,digital health literacy,technological accessibility,and supporting environment and resources.Antecedents can be discussed from the aspects of digital gap,health care service,and user factors.Mobile health readiness can impact on users and health care systems.Conclusion The concept attributes of mobile health readiness were identified by concept analysis method,which provides references for community nurses to assess the mobile health readiness of users.In the future,researchers can combine the connotations of mobile health readiness to develop assessment tools,and construct interventions for the implementation of mobile health,thereby promoting the application of mobile health in China and the development of intelligent nursing.

Objective     To investigate the perioperative clinical effects and follow-up results of minimally invasive coronary artery bypass grafting (MICS CABG) versus conventional coronary artery bypass grafting (CABG) in thoracotomy. Methods     The patients who received off-pump CABG in Beijing Anzhen Hospital from January 2017 to October 2021 were collected. Among them, the patients receiving MICS CABG performed by the same surgeon were divided into a minimally invasive group, and the patients receiving median thoracotomy were into a conventional group. By propensity score matching, preoperative data were balanced. Perioperative and postoperative follow-up data of the two groups were compared. Results     A total of 890 patients were collected. There were 211 males and 28 females, aged 60.54±9.40 years in the minimally invasive group, and 487 males and 164 females, aged 62.31±8.64 years in the conventional group. After propensity score matching, there were 239 patients in each group. Compared with the conventional group, patients in the minimally invasive group had longer operation time, shorter drainage duration, less drainage volume on the first postoperative day, shorter postoperative hospital stay, and lower rate of positive inotropenic drugs use, while there was no statistical difference in the mean number of bypass grafts, ICU stay, ventilator-assisted time, blood transfusion rate or perioperative complications (P>0.05). During the median follow-up of 2.25 years, there was no statistical difference in major adverse cardiovascular and cerebrovascular events, including all-cause death, stroke or revascularization between the two groups (P>0.05). Conclusion    Reasonable clinical strategies can ensure perioperative and mid-term surgical outcomes of MICS CABG not inferior to conventional CABG. In addition, MICS CABG has the advantages in terms of postoperative hospital stay, postoperative drainage volume, and rate of positive inotropic drugs use.

Traditional Chinese medicine(TCM) compound preparations have complex compositions. As a widely used TCM injection, Shuganning Injection, its in vivo processes are not yet fully understood. Determining the plasma protein binding rate is of great significance for pharmacokinetic and pharmacodynamic studies. In this experiment, the equilibrium dialysis method combined with UPLC-MS/MS technology was used to determine the plasma protein binding rates of 10 components, including p-hydroxyacetophenone, caffeic acid, baicalein, oroxylin A, geniposide, baicalin, cynaroside, oroxylin A-7-O-β-D-glucuronide, scutellarin, and hyperoside, in Shuganning Injection in rat and human plasma to provide a theoretical basis for further elucidating the in vivo processes of Shuganning Injection and guiding clinical medication. The results showed that, except for baicalein and geniposide, the plasma protein binding rates of the other eight components were higher in human plasma than in rat plasma, and there were interspecies differences. In human plasma, except for geniposide, caffeic acid, and baicalin, the plasma protein binding rates of the remaining seven components were above 80%, with baicalein and oroxylin A exceeding 90%. All components exhibit a high level of binding to plasma proteins, with the exception of geniposide.
Rats ; Humans ; Animals ; Tandem Mass Spectrometry/methods* ; Chromatography, Liquid/methods* ; Rats, Sprague-Dawley ; Liquid Chromatography-Mass Spectrometry ; Protein Binding ; Renal Dialysis ; Drugs, Chinese Herbal ; Blood Proteins ; Chromatography, High Pressure Liquid/methods*

Objective: To establish the norms and clinical application standards of mass spectrometry method to measure vitamin D in capillary blood. Methods: Following the "Province-City-Hospital" sampling procedure, a cross-sectional sample of 1 655 healthy children under 7 years of age were recruited from 12 provinces, autonomous regions, or municipalities in China from November 2020 to December 2021. Both venous and capillary blood samples from the same individual were collected, for which serum 25(OH)D levels were measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. Pearson correlation analysis and linear regression analysis were used to detect the correlation and determine a correction algorithm. The agreement was analyzed using Bland-Altman plot and Kappa statistic. The sensitivity and specificity were evaluated using receiver operating characteristic (ROC) curve method. Results: Venous and capillary 25(OH)D levels of 1 655 healthy children under 7 years of age were 74.25 (59.50, 92.00) and 68.75 (54.44, 86.25) nmol/L, respectively, showed a significant difference(Z=22.14, P<0.001) as well as a highly significant correlation between venous and capillary 25(OH)D levels(r=0.95, P<0.001). Linear regression analysis was then performed to determine the correction algorithm: lg(corrected capillary 25(OH)D)=0.13+0.95×lg(capillary 25(OH)D)(R²=0.90,P<0.001). The deviation between venous and corrected capillary 25(OH)D levels was (0.50±17.50) nmol/L, a difference value that did not reach statistical significance (P>0.05). The cut-off values of capillary blood 25(OH)D values 30.00, 50.00, 75.00 nmol/L corresponding to venous blood 25(OH)D values were 26.59, 45.56, and 69.84 nmol/L, respectively. Good consistency was observed between venous and corrected capillary 25(OH)D levels in clinical diagnosis (Kappa value 0.68-0.81). Corrected capillary 25(OH)D showed a high clinically predictive value (area under curve 0.97-0.99,sensitivity 0.72-0.92,specificity 0.89-0.99). Conclusion: The standardized capillary HPLC-MS/MS method can be used to detect 25(OH)D levels in children clinically.
Child ; Humans ; Vitamin D ; Cross-Sectional Studies ; Tandem Mass Spectrometry ; Vitamins ; Reference Standards

OBJECTIVE: To investigate the feasibility of using thyroid ^99mTcO₄^- imaging ROI ratio instead of 24 h radioactive iodine uptake (RAIU) for estimating ¹³¹I dose in individualized treatment of hyperthyroidism. METHODS: We retrospectively analyzed the clinical data of 132 patients receiving ¹³¹I treatment in our department between January and June, 2019. According to their 3 h/24 h RAIU peak ratio, the patients were divided into peak forward (≥80%) group and no peak forward (< 80%) group. In the former group, the therapeutic ¹³¹I dose was calculated based the Marinelli formula (¹³¹I dose=thyroid mass×planned amount/24 h RAIU), and in the latter group, the correlation between the ROI ratio and the 24 h RAIU was analyzed, and the ¹³¹I dose was calculated using a modified Marinelli formula where 24 h RAIU was replaced by a converted ROI ratio. The two groups of patients were compared for antithyroid drug type and discontinuation time, thyroid hormones and related antibodies, thyroid area, thyroid mass and ¹³¹I dose. All the patients were and followed up for one year to analyze the treatment efficacy. The ROI ratios after the treatment were analyzed in the two groups using ROC curves. RESULTS: There was a significant positive correlation between the ROI ratio and 24 h RAUI in the no peak forward group (Y=58.13 + 0.2X, R²=0.118, P < 0.05), and the formula for calculating ¹³¹I dose was converted into: ¹³¹I dose=thyroid mass× planned amount/(58.13+0.2×ROI ratio)%. Before the treatment, therapeutic ¹³¹I dose, thyroid hormone levels, TRAb, 3 h and 24 h RAIU, thyroid area, thyroid mass, and ROI ratio all differed significantly between the two groups (P < 0.05). At 3 months after treatment, thyroid hormone levels, TRAb, TPOAb, thyroid area, thyroid mass, ROI ratio, response rate, hypothyroidism rate, cure rate, remission rate, and nonresponse rate were similar between two groups (P>0.05). At the 1-year follow-up, the composition ratios of hyperthyroidism, hypothyroidism and cured cases remained similar between two groups (P>0.05). ROC curve analysis showed that at 3 months after treatment, the optimal cutoff values of ROI ratio for predicting hyperthyroid recurrence and hypothyroidism were 15.79 and 6.33, respectively. CONCLUSION Thyroid ^99mTcO₄^- imaging ROI ratio can be used for calculating ¹³¹I dose in individualized treatment of hyperthyroidism and for prognostic evaluation of the patients.
Humans ; Iodine Radioisotopes/therapeutic use* ; Retrospective Studies ; Thyroid Neoplasms ; Hypothyroidism