BackgroundLow medication compliance among patients with severe mental disorders increases the disease burden on both the patients' families and the society. Medication adherence is influenced by numerous factors. Traditional methods such as Logistic regression struggle to quantify the importance of these factors. By introducing Extreme Gradient Boosting （XGBoost） combined with Shapley Additive Explanations （SHAP）， enables the quantification of the relative contribution weights of each factor， providing support for identifying the core influencing factors. ObjectiveTo explore the influencing factors of medication adherence among patients with severe mental disorders in Zhuhai， aiming to provide references for optimizing patient management strategies. MethodsExtract the data of patients with severe mental disorders who were registered on the mental health system platform in Zhuhai City from January 1， 2023 to March 31， 2025. A total of 9 329 patients were finally included for analysis. Influencing factors were screened using univariate analysis and multivariate logistic regression analysis， and an XGBoost model combined with the SHAP algorithm was constructed to quantify the importance of each influencing factor. ResultsAmong 9 329 patients， 8 446 demonstrated medication adherence， yielding an adherence rate of 90.53%. Multivariable analysis identified several risk factors significantly associated with medication non-adherence， being unmarried （OR=1.237， 95% CI： 1.019–1.502） or divorced （OR=1.389， 95% CI： 1.038–1.832）， a diagnosis of mental retardation with psychiatric disorders （OR=3.025， 95% CI： 2.402–3.796） or paranoid psychosis （OR=5.117， 95% CI： 3.086–8.299）， a disease duration of 2–4 years （OR=1.355， 95% CI： 1.085–1.696）， 4–6 years （OR=2.143， 95% CI： 1.671–2.747）， or >6 years （OR=1.681， 95% CI： 1.365–2.079）， lack of guardian subsidies （OR=1.412， 95% CI： 1.099–1.801）， absence of a disability certificate （OR=1.900， 95% CI： 1.588–2.282）， not being enrolled in care and support groups （OR=1.384， 95% CI： 1.183–1.617） or community services （OR=1.313， 95% CI： 1.042–1.645）， and not cohabiting with a guardian （OR=1.257， 95% CI： 1.048–1.501）. Conversely， the enrollment in special outpatient disease programs （OR=0.716， 95% CI： 0.609–0.842） and a family history of mental illness （OR=0.713， 95% CI： 0.503–0.982） were identified as protective factors. The XGBoost model exhibited robust predictive performance， with a sensitivity of 0.433， specificity of 0.944， accuracy of 0.891， Area Under the Curve （AUC） of 0.837， and F1 value of 0.449. Feature importance ranking indicated that the top three factors were disease duration， diagnosis， and the acquisition of disability certificates. ConclusionPolicy-based support （acquisition of disability certificates， special outpatient disease enrollment） and clinical disease characteristics （disease duration， diagnosis type） are key factors affecting medication adherence among patients with severe mental disorders in Zhuhai City. ［Funded by Zhuhai Medical Research Project （number， 2220009000281）］

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and joint destruction. Iguratimod (IGU) is a novel conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with good efficacy and safety for the treatment of active RA in China and Japan. However, the long-term effects of IGU on the progression of bone destruction or radiographic progression in patients with active RA remain unknown. We aimed to investigate the efficacy and safety of iguratimod (IGU), a combination of methotrexate (MTX) and IGU, and IGU in patients with active rheumatoid arthritis (RA) who were naïve to MTX. METHODS: This multicenter, double-blind, randomized, non-inferiority clinical trial was conducted at 28 centers for over 52 weeks in China. In total, 911 patients were randomized (1:1:1) to receive MTX monotherapy (10-15 mg weekly, n = 293), IGU monotherapy (25 mg twice daily, n = 297), or IGU + MTX (10-15 mg weekly for MTX and 25 mg twice daily for IGU, n = 305) for 52 weeks. The patients' clinical characteristics, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), disease activity score in 28 joints-C-reactive protein (DAS28-CRP) level, and disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) were assessed at baseline. The primary endpoints were the proportion of patients with ≥20% improvement according to the American College of Rheumatology (ACR20) response and changes in the van der Heijde-modified total Sharp score (vdH-mTSS) at week 52. RESULTS: The proportions of patients achieving an ACR20 response at week 52 were 77.44%, 77.05 %, and 65.87% for IGU monotherapy, IGU + MTX, and MTX monotherapy, respectively. The non-inferiority of IGU monotherapy to MTX monotherapy was established with the ACR20 (11.57%; 95% confidence interval [CI], 4.35-18.79%; P <0.001) and vdH-mTSS (-0.37; 95% CI, -1.22-0.47; P = 0.022). IGU monotherapy was also superior to MTX monotherapy in terms of ACR20 ( P = 0.002) but not the vdH-mTSS. The superiority of IGU + MTX over MTX monotherapy was confirmed in terms of the ACR20 (11.18%; 95% CI, 3.99-18.37%; P = 0.003), but not in the vdH-mTSS (-0.68; 95% CI, -1.46-0.11; P = 0.091). However, the difference in the incidence rates of adverse events was not statistically significant. CONCLUSIONS: IGU monotherapy/IGU + MTX showed a more favorable clinical response than did MTX monotherapy. IGU may have some clinical benefits over MTX in terms of radiographic progression, implying that IGU may be considered as an initial therapeutic option for patients with active RA. TRIAL REGISTRATION https://classic.clinicaltrials.gov/ , NCT01548001.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Chromones/adverse effects* ; Double-Blind Method ; Drug Therapy, Combination ; Methotrexate/adverse effects* ; Treatment Outcome ; Sulfonamides

Nanotechnologies seek to overcome inherent deficiencies of conventional diagnosis and treatment, which attracted sustained attention and a limited number of nanomedicines approved by the FDA. However, the critical gaps in clinical translation remain, and nanomedicines that were initially heralded as magic bullets have yet to reach their realistic potential. The major obstacles of fabrication technologies may be overlooked in the nanoparticles' journey. Suboptimal manufacturing strategies partly hampered the inefficient transformation. In this review, we discuss the nanoparticle manufacturing strategies of "Top-Down" and "Bottom-Up" on precise nanoscale fabrication, including artificial intelligence introduced to guided nanomedicine fabrication for accelerating the transformation. Re-engineering existing nanomedicine fabrication, individual manufacturing, and modular technology might highlight the dilemmas of nanomedicines to meet their initial expectations.

Objective To investigate the predictive value of β3-adrenergic receptor(β3-AR)expression levels for recurrence after radiofrequency ablation in patients with atrial fibrillation(AF).Methods Patients with AF who underwent their first radiofrequency ablation in the Department of Cardiology from January 2022 to February 2024(AF group,n=166)and healthy individuals undergoing routine medical check-ups during the same period(control group,n=100)were selected as study subjects.Based on whether AF recurred after the procedure during follow-up,AF patients were divided into a non-recurrence group and a recurrence group.General clinical data and relevant laboratory indices of AF patients were collected.The relative expression lev-el of lymphocyte β3-AR mRNA was measured using fluorescence real-time quantitative PCR.Multivariate lo-gistic regression analysis was used to identify risk factors for AF recurrence after surgery,and receiver operat-ing characteristic(ROC)curve analysis was employed to evaluate the predictive value of β3-AR mRNA ex-pression levels for AF recurrence after ablation.Results After 9 months of follow-up post-radiofrequency ab-lation,among 166 AF patients,42 experienced recurrence,with a recurrence rate of 25.3%.Compared with the non-recurrence group,patients in the recurrence group had significantly higher levels of sST2,IL-6 and left at-rial diameter(LAD),with a statistically significant differences(P<0.05).The relative expression level of β3-AR was higher in the recurrence group than in the non-recurrence group,with a statistically significant differ-ence(P<0.05).Multivariate logistic regression analysis showed that LAD,sST2,IL-6,and β3-AR were inde-pendent risk factors for AF recurrence after surgery(P<0.05).ROC curve analysis indicated that the area under the curve for β3-AR mRNA relative expression level in predicting AF recurrence after radiofrequency ablation was 0.884(95%CI:0.794 to 0.975;P<0.05).Conclusion High preoperative expression levels of β3-AR in AF patients are associated with recurrence after radiofrequency ablation,and β3-AR can serve as a potential biological marker for predicting AF recurrence.

Objective To observe the clinical efficacy and safety of nivolumab combined with anlotinib in the treatment of patients with advanced gastric cancer.Methods The patients with advanced gastric cancer were randomly divided into control group and treatment group.The control group received oral apatinib capsules 12 mg,once a day,and discontinued treatment for 7 days after 14 days of maintenance therapy.On the basis of control group,the treatment group received intravenous infusion of 3 mg·kg-1 nivolumab,once every two weeks.Two groups were treated for four cycles with 21 days per cycle.The clinical efficacy,tissue polypeptide specific antigen(TPS),carbohydrate antigen 125(CA125),carcinoembryonic antigen(CEA)and adverse drug reactions were compared between two groups.Results In the treatment group,80 cases were enrolled,and 4 cases dropped out and 76 cases were included in the statistical analysis;in the control group,80 cases were enrolled,and 8 cases dropped out and 72 cases were included in the statistical analysis.After treatment,the total effective rates in the treatment and control group weres 78.95％(60 cases/76 cases)and 52.78％(38 cases/72 cases),and the difference was statistically significant(P＜0.05).After treatment,the levels of CEA in the treatment and control groups were(5.34±1.12)and(7.01±0.97)U·mL-1;the levels of CA125 were(22.65±4.27)and(27.61±5.09)U·mL-1;the levels of TPS were(69.21±11.64)and(53.06±10.57)U·mL-1;these differences were statistically significant(all P＜0.05).The adverse drug reactions of two groups were nausea/diarrhea,leukopenia,thrombocytopenia,abnormal liver function,and hypothyroidism.The total incidences of adverse drug reactions in the treatment and control groups were 40.79％and 37.50％without statistically significant difference(P＞0.05).Conclusion Ramucirumab injection combined with anlotinib capsules is more effective than single-agent anlotinib in the treatment of advanced gastric cancer,without increasing the incidence of adverse drug reactions.

BACKGROUND:Adjustable piezoelectric effect can promote tissue regeneration and repair.Piezoelectric materials are widely used in weight-bearing tissue engineering. OBJECTIVE:To prepare a piezoelectric film material that can promote bone regeneration,and to explore its structural characterization,electrical output performance,biocompatibility,and effect of electrical output on osteogenic differentiation of rabbit bone marrow mesenchymal stem cells. METHODS:Using poly-3-hydroxybutyrateco/4-hydroxybutyrate(P34HB)as raw material,barium calcium stannate titanate powder(Ba0.94Ca0.06Sn0.08Ti0.92O3,BCST)was added according to mass ratios of 0%,5%,10%,15%,and 20%.Dichloromethane was added to solve P34HB,and the thickness of 150-200 μm BCST/P34HB piezoelectric film was prepared by vacuum drying method.After polarization in the oil bath,the surface morphology,crystal phase composition,piezoelectric coefficient and open circuit voltage were tested.The effect of BCST/P34HB electrical output at 110 Hz and 0.25 N force on the proliferation and osteogenic differentiation of rabbit bone marrow mesenchymal stem cells was tested. RESULTS AND CONCLUSION:(1)Scanning electron microscopy,X-ray diffraction,water contact angle,piezoelectric coefficient and electrical output performance tests showed that when the mass ratio of BCST increased to 20%,the BCST/P34HB piezoelectric film had good piezoelectric properties(d33=5.9 pC/N)and electrical output performance(180 mV),which was closer to the suitable range of 500 mV for electrical stimulation.(2)Live and dead staining showed that on the first day of co-culture,15%group and 20%group showed less red fluorescence.On the 5th day of culture,the number of green fluorescence in each group was significantly higher than that on the first day,and the red fluorescence was not observed in the 10%,15%and 20%groups,and only a small amount of red fluorescence was observed in the 0%and 5%groups.(3)On the 1st,3rd and 5th days of co-culture with rabbit bone marrow mesenchymal stem cells,Almar blue staining exhibited that the number of cells in each group showed an increasing trend with the increase of time.On the 5th day of culture,the number of cells in the 20%group was significantly more than that in the 0%group(P<0.05).(4)On day 10 of osteogenic induction,alkaline phosphatase staining results showed that the positive rate of the 20%group was significantly higher than that of the 0%group(P=0.000 1).On day 21,alizarin red staining and quantitative analysis of calcium nodules showed a similar trend to alkaline phosphatase staining.Compared with the 0%group,the 15%group and 20%group showed significant differences(P<0.01,P<0.000 1).(5)The results showed that 20%BCST/P34HB films had good piezoelectric properties,electrical output properties,biocompatibility and the ability of promoting osteogenic differentiation of bone marrow mesenchymal stem cells.

Objective:To retrieve, evaluate and integrate the relevant evidence of prevention of lower limb ischemic complications in venous-arterial extracorporeal membrane oxygenation (VA-ECMO) patients, and provide reference for the development of scientific and complete prevention and management of lower limb ischemic complications.Methods:According to the evidence-based methodology, clinical decisions, guidelines, expert consensus, evidence summary, systematic review, randomized controlled trials and experimental studies related to lower limb ischemia complications in VA-ECMO patients were searched from CNKI, Wanfang, PubMed, Cochrane Library and other domestic and foreign databases as well as relevant professional websites. The literature search period was from the establishment of the database to August 2023. Two researchers independently evaluated the literature quality, and then extracted and summarized the evidence according to the theme.Results:A total of 27 004 articles were obtained in the preliminary search, and 11 articles were finally included after screening, including 1 guide, 2 expert consensus, 2 systematic reviews and 6 original studies. Through literature reading, evidence extraction and classification, and expert group meetings, a total of 24 best evidences were concluded in four dimensions, including team training and management, VA-ECMO pre-computer evaluation, VA-ECMO catheter selection, and the monitoring and management of lower limb ischemia.Conclusions:This study summarized the best evidence for the prevention of lower limb ischemia complications associated with VA-ECMO patients, and can provide reference for healthcare providers in clinical practice. In order to ensure the safety of VA-ECMO treatment and reduce the incidence of related complications, healthcare professionals should carefully select and apply evidence according to the clinical context and patients′ wishes.

Objective Hippocampal atrophy is a clinically important marker for the diagnosis of many psychiatric disorders such as Alzheimer’s disease‚ so accurate segmentation of the hippocampus is an important scientific issue. With the development of deep learning‚ a large number of advanced automatic segmentation method have been proposed. However‚ 3D hippocampal segmentation is still challenging due to the effects of various noises in MRI and unclear boundaries between various classes of the hippocampus. Therefore‚ the aim of this paper is to propose new method to segment the hippocampal head‚ body‚ and tail more accurately. Methods To overcome these challenges‚ this paper proposed two strategies. One was the spatial and frequency domain features adaptive fusion strategy‚ which reduced the influence of noise on feature extraction by automatically selecting the appropriate frequency combination through fast Fourier transform and convolution. The other was an inter-class boundary region enhancement strategy‚ which allowed the network to focus on learning the boundary regions by weighting the loss function of the boundary regions between each class to achieve the goal of pinpointing the boundaries and regulating the size of the hippocampal head‚ body and tail. Results Experiments performed on a 50-case teenager brain MRI dataset show that our method achieves state-of-the-art hippocampal segmentation. Hippocampal head‚ body and tail had been improved compared to the existing method. Ablation experiments demonstrated the effectiveness of our two proposed strategies‚ and we also validated that the network had a strong generalization ability on a 260-case Task04_Hippocampus dataset. It was shown that the method proposed in this paper could be used in more hippocampal segmentation scenarios. Conclusion The method proposed in this paper can help clinicians to observe hippocampal atrophy more clearly and accomplish more accurate diagnosis and follow-up of the condition.

Objective To evaluate the application effect of broth microdilution(BMD)method in susceptibility testing of multidrug-resistant Mycobacterium tuberculosis(MDR-MTB).Methods The Roche's proportion method and BMD method were adopted in drug susceptibility testing on 108 MDR-MTB strains and 11 non-MDR-MTB strains in Hainan Province.Whole genome sequencing(WGS)was performed on strains with inconsistent results by the above two methods.Results The average time to acquire drug susceptibility testing results by Roche's propor-tional method and BMD method were 28.0 and 8.5 days,respectively.Roche's proportional method showed higher resistance rates to isoniazid(INH),rifampicin(RFP),ethambutol(EMB),kanamycin(KM),and capreomycin(CPM)than BMD method(all P＜0.001).BMD method showed higher resistance rates to protionamide(PTO)and para-aminosalicylic acid(PAS)than Roche's proportional method(both P＜0.001).Taking Roche's proportional method as the gold standard,the sensitivity and specificity of BMD method for testing drug resistance were 50.00％-100％and 95.69％-100％,respectively.Except EMB(87.39％)and INH(94.96％),the consistency rates of the BMD method in testing drug resistance of other drugs were all ≥95.00％.The overall consistency rate between Roche's proportional method and WGS was 76.19％(32/42),while the consistency rate between BMD method and WGS was 23.81％(10/42),difference was statistically significant(x2=23.048,P＜0.001).34 MTB strains showed inconsistent results by two drug susceptibility testing methods.Among the 26 MTB strains that were resis-tant in Roche's proportion method but sensitive in BMD method,22 strains(84.62％)had mutations in relevant re-sistance genes.Among the 11 MTB strains that were sensitive in Roche's proportion method but resistant in BMD method,5 strains(45.45％)had mutations in relevant resistance genes.Conclusion BMD method is an accurate and rapid MDR-MTB susceptibility testing method,but further improvement and optimization are still needed.Drug resistance is closely related to mutations in relevant resistance genes.

Objective To observe and compare the concentrations of tryptophan-kynurenine pathway metabolites in serum and urine of adolescents with depression individuals using liquid chromatography-tandem mass spectrometry(LC-MS/MS).Methods The major metabolites in this pathway,such as tryptophan(TRP),kynurenine(KYN),kynurenic acid(KYNA),and 3-hydroxykynurenine(3-HK)were quantitatively analyzed using isotope-labeled internal standards.The separation was achieved using a Shimadzu C18 col-umn with gradient elution of 0.2％aqueous acid and acetonitrile.The detection was performed within 7 minutes using positive ion mode and multiple reaction monitoring(MRM).The parameters,such as linear range and precision were evaluated to assess reliability of the method.Subsequently,this method was applied to detect and compare the results in the samples of serum and urine from 143 adoles-cents with depression and 110 healthy controls.Results Taking TRP as the example,the linear ranges for serum and urine were 0.54 to 107.84 μmol/L and 0.74 to 147.06 μmol/L,respectively.The intra-batch coefficient of variation(CV)was ≤6.3％,the inter-batch CV was ≤3.22％,and the total laboratory CV was ≤6.5％.The results showed the KYNA,KYN and TRP levels were lower in the de-pression group compared to the control group,while 3-HK levels were higher in the depression group with statistical significance(P＜0.01).Apart from TRP,the levels of other metabolites were significantly higher in urine than those in serum,with statistical signifi-cance(P＜0.01).Conclusion Compared to the results of serum,the concentrations of TRP metabolites,including KYN,KYNA and 3-HK were higher than those in urine.The concentrations of TRP-KP metabolites in urine,i.e.,KYN,KYNA and 3-HK were higher than those in serum,and the detection of TRP-KP metabolites in urine may offer a greater advantage because the urine collection process is non-invasive.