Enzymatic cascade catalysis has emerged as an effective means to enhance the sensitivity of biosensors due to its remarkable amplification effect on electrochemical signals.However,the most used natural enzymes have high specificity and high catalytic activity,but are susceptible to environmental factors,easy denaturation and inactivation,and high cost,which limit their practical applications.Additionally,the majority of nanozymes with excellent catalytic activity cannot be directly used as redox probes.The redox signal can only be required under high potentials in strong acid/alkali solutions,or functionalized with electroactive substances.To tackle this problem,herein,AuNPs(glucose oxidase-like activity)and Mn,Zr dual-doped CeO2 nanozymes(Mn,Zr-CeO2,peroxidase-like activity)were used as model enzymes to construct a high-performance nanozymes cascade catalytic system.Owing to high Ce4+/Ce3+ratio and a considerable number of oxygen vacancies,Mn,Zr-CeO2 nanozymes exhibited excellent peroxidase-like activity and could generate amplified electrochemical signals in neutral medium at low potentials.Furthermore,the porous structure of Mn,Zr-CeO2 nanozymes could accelerate the mass transfer of intermediate H2O2,thereby enhancing the efficiency of enzymatic cascade catalysis.As a result,a label-free electrochemical biosensor was constructed for sensitive detection of the cancer marker miRNA-21 at physiological pH,with a detection limit as low as 32.5 fmol/L.This strategy offered a novel approach for the development of a new generation of high-performance nanozymes cascade platforms,which could be widely applied in the fields such as biotechnology,bioanalysis,and disease diagnosis.

Objective To investigate the association between rest-activity rhythm(RAR)and the risks of rheumatoid arthritis(RA),and to evaluate whether genetic susceptibility modifies this relationship.Methods This prospective cohort study utilized data from the UK Biobank,including 88 060 participants who did not have RA at baseline.RAR parameters(e.g.,relative amplitude)were calculated using data obtained through wrist-worn accelerometers.The participants'genetic susceptibility to RA was assessed using a polygenic risk score.Cox proportional hazards models were employed to analyze the association between RAR and RA risk,with interaction terms incorporated to evaluate the effect modification by genetic susceptibility.Results Over a median follow-up period of 7.97 years,660 incident RA cases were identified.After adjusting for age,sex,ethnicity,educational attainment,Townsend deprivation index,drinking status,smoking status,dietary score,body mass index,and polygenic risk score for incident RA,the dose-response analysis revealed a linear relationship between the RAR-related parameters,including the average amplitude during the most active 10 h(M10),interdaily stability(IS),intradaily variability(IV),and the risk of developing RA(P>0.05).In contrast,relative amplitude and the average amplitude during the least active 5 h(L5)showed a nonlinear relationship with the risk of developing RA(P<0.05).Compared to those in the the highest quartile of relative amplitude,participants in the lowest quartile had a 49%increase in the risk of developing RA(hazard ratio[HR]=1.49;95%CI,1.17-1.90).Compared to those in the lowest quartile,participants in the highest quartile of L5 had a 40%increased risk of developing RA(HR=1.40;95%CI,1.12-1.75).Every time M10 increased by one standard deviation,the risk of developing RA decreased by 12%(HR=0.88;95%CI,0.80-0.96).No evidence of effect modification by genetic susceptibility was observed in the RAR-RA association(P>0.05).Conclusion Disrupted rest-activity rhythm is associated with an increased risk of RA,which is independent of genetic susceptibility to RA.Our findings suggest that improving rest-activity rhythm may help reduce RA risks.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.

Objective:To address the critical issue of missing dynamic border molding information in edentulous direct digital impression technology, this study explores innovative digital solutions and conducts preliminary application validation.Methods:Based on the myostatic line theory, a methodology was established: intraoral scanner (IOS) high-frequency video was utilized to dynamically capture functional molding data of soft tissues, integrated with a self-developed mobility gradient recognition algorithm to achieve dynamic threshold segmentation between the muscle dynamic zone and myostatic zone, termed "optical digital molding technology". Ten edentulous patients with well-fitting complete dentures, treated at the Department of Prosthodontics, Peking University School and Hospital of Stomatology from January 2024 to December 2024, were enrolled. The standard deviation between the muscle static line (generated by mobility gradient algorithm with thresholds of 0.3-0.7 mm) and the denture border curve was analyzed to optimize the dynamic threshold, followed by single-case clinical validation.Results:Among the mobility thresholds of 0.3-0.7 mm, the 0.5 mm threshold yielded the smallest standard deviation between the myostatic line and denture border. Clinical validation demonstrated that dentures designed with this threshold exhibited no displacement during dynamic functional tests, with marginal sealing meeting clinical standards.Conclusions:The optical digital border molding technique for edentulous soft tissue boundaries translates the myostatic line theory into quantifiable parameters for the first time. Based on data from 10 cases, a mobility threshold of 0.5 mm is recommended for clinical application.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*

This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history* ; Humans ; Medicine, Chinese Traditional/history* ; History, Ancient ; Astragalus Plant/chemistry* ; China ; Astragalus propinquus

OBJECTIVE: To investigate the efficacy and safety of oblique lateral interbody fusion(OLIF) channel technique combined with pedicle screw internal fixation in the treatment of single-segment lumbar intervertebral space/vertebral body infection. METHODS: A retrospective analysis was conducted on 23 patients who underwent surgical treatment for lumbar infection from January 2021 to December 2022. The patients were divided into the OLIF channel group and the traditional open surgery group according to the surgical methods. There were 16 cases in the OLIF channel group, including 9 males and 7 females, with an average age of (68.5±12.1) years old;there were 7 cases in the traditional open surgery group, including 4 males and 3 females, with an average age of (75.0±3.2) years old. The operation time, intraoperative blood loss, hospital stay, incision length, visual analogue scale(VAS), activities of daily living (ADL) score, Oswestry disability index (ODI), erythrocyte sedimentation rate(ESR), C-reactive protein(CRP) before and 1 week and 3 months after the operation, and the intervertebral fusion status on the last follow-up CT were compared between the two groups. RESULTS: Compared with the open surgery group, the OLIF channel group had shorter operation time (209.87±31.5) min vs. (246.0±42.7) min, less intraoperative blood loss (225.625±91.1) ml vs. (364.2±74.8) ml, and shorter incision length (6.1±1.2) vs. (14.0±1.4) cm, and the differences were statistically significant(P<0.05). Before and 1 week and 3 months after the operation, the lumbar VAS in the OLIF group were (6.3±0.6), (2.8±0.7), (1.1±0.5), and those in the traditional open surgery group were (6.4±0.6), (3.4±0.5), (1.2±0.3);the ADL scores in the OLIF group were (45.0±4.5), (60.3±4.3), (94.1±4.2), and those in the open group were (46.4±5.6), (60.7±4.5), (92.9±4.9); the ODI scores in the OLIF group were (86.3±2.9)%, (69.5±4.1)%, (23.0±3.2)%, and those in the open group were (87.3±3.8)%, (69.8±4.2)%, (23.8±3.6)%, all of which showed significant improvement(P<0.05). Three months after the operation, CRP, PCT, and ESR were significantly lower than those before the operation, and CRP and PCT returned to normal, while ESR was still slightly elevated in some patients. The last follow-up CT showed that continuous trabecular bone formation was observed between the upper and lower endplates of the surgical segments in all patients, and the fusion time was (8.7±4.5) months. CONCLUSION The OLIF channel technique combined with posterior internal fixation is a minimally invasive and effective treatment method, which can effectively control infection, relieve pain, and improve the quality of life of patients. Compared with traditional open surgery, it has the advantages of minimally invasive, shorter operation time, and less intraoperative blood loss.
Humans ; Male ; Female ; Spinal Fusion/methods* ; Lumbar Vertebrae/microbiology* ; Aged ; Middle Aged ; Retrospective Studies ; Aged, 80 and over ; Pedicle Screws ; Infections/surgery*