Introduction: A significant proportion of severe asthma patients require oral corticosteroids (OCS) to maintain symptom control. Prolonged OCS predisposes patients to hypothalamicpituitary-adrenal axis suppression which can be lifethreatening. Biologic therapies are effective steroid-sparing options suitable for select severe asthma patients. We evaluated steroid tapering outcomes and adrenal function during biologic therapy in a tertiary severe asthma clinic. Results: A total of 43 patients were included. Median age was 66 years (interquartile range [IQR] 60–74), and 65% were male. Mepolizumab was the most used (17 patients), followed by benralizumab (15), tezepelumab (6), dupilumab (4), and omalizumab (1). Median baseline prednisolone dose was 10 mg (IQR 5–10). Median lowest dose achieved was 3 mg (IQR 0–3), sustained for at least 4 weeks in 90.7% of patients. Median reduction in prednisolone dose was 5 mg (IQR 5–7.25). In all, 42% of patients successfully discontinued maintenance steroids. Adrenal function was assessed using morning serum cortisol (n = 37) and/or SST (n = 28). Evidence of adrenal insufficiency was identified in 19 patients (44%), including 15 patients with failed SST and four with low morning cortisol suggestive of adrenal suppression. Morning serum cortisol was indeterminate in four patients. A total of 17 patients were referred to endocrinology. During steroid tapering, 11 asthma-related hospital admissions and eight emergency department presentations occurred, involving 10 patients. Conclusion Biologics facilitate the reduction of the OCS burden in severe asthma. Tertiary adrenal suppression is common during steroid tapering and requires prompt biochemical assessment and endocrinology referral. Structured monitoring of adrenal function is essential during biologicfacilitated steroid tapering in routine clinical practice.
Biological Products ; Steroids ; Asthma

Objective To develop a diagnostic model combining the CT angiography(CCTA)-derived myocardial radiomics signatures with the CT-derived fractional flow reserve(CT-FFR)based on coronary CCTA and investigate the diagnostic accuracy of the hybrid model for hemodynamically significant coronary artery disease(CAD).Methods The patients presenting stable angina pectoris,diagnosed with CAD,and clinically referred for CCTA examination and invasive coronary angiography were prospectively recruited.Radiomics features of the left ventricular myocardium were extracted from the three main perfusion territories demarcated according to the coronary blood supply.The extracted features were first selected by the minimum redundancy maximum relevance feature ranking method.A least absolute shrinkage and selection operator Logistic regression algorithm with leave-one-out cross-validation was then employed to construct a radiomics model.The CT-FFR value was generated for each blood vessel.The area under the receiver operating characteristics curve(AUC_ROC),sensitivity,and specificity were adopted to evaluate the performance of each model against the reference standard invasive coronary angiography/FFR.Results A total of 70 patients[42 men and 28 women;(61±10) years old] were included in this study and complemented CCTA examination,with 175 vessels and the corresponding myocardial territories undergoing invasive coronary angiography/FFR.A total of 1 656 specific radiomics parameters were extracted,from which 14 features were selected to establish the radiomics model.The AUC_ROC,sensitivity,and specificity were 0.797(95%CI=0.732-0.861),77.1%,and 73.7%for the radiomics model,0.892(95%CI=0.841-0.943),81.4%,and 88.8%for the CT-FFR model,and 0.928(95%CI=0.890-0.965),83.3%,and 88.4%for the hybrid model,respectively.The hybrid model outperformed the radiomics model and CT-FFR alone(P=0.040).Conclusions The radiomics signatures of the vessel-related myocardium from CCTA could provide incremental value to the diagnostic performance of CT-FFR and improve vessel-specific ischemia detection.The hybrid model combining CT-FFR with radiomics signatures is potentially feasible for improving the diagnostic accuracy for hemodynamically significant CAD.
Coronary Angiography/methods* ; Tomography, X-Ray Computed ; Humans ; Hemodynamics ; Coronary Artery Disease/diagnostic imaging* ; Male ; Female ; Middle Aged ; Aged ; Radiomics ; Angina Pectoris/diagnostic imaging* ; China ; Image Processing, Computer-Assisted ; Coronary Vessels/diagnostic imaging*

Aerosol-assisted plasma amplification laser-induced breakdown spectroscopy(LIBS)was employed for phosphorus detection in water.To address the multivariate coupling effects in LIBS and nebulization sampling system,an orthogonal experiment was employed to systematically optimize the key experimental parameters.Using the orthogonal experimental design,the parametric effects of laser energy(output voltage),signal acquisition delay,liquid velocity,and gas velocity on the signal to background ratio(SBR)of P I 213.618 nm were evaluated,and the optimal conditions were achieved,including laser energy of 86 mJ,delay time of 3 μs,gas velocity of 1.05 mL/min,and liquid velocity of 60 μL/min,which were in agreement with the control-variable optimization results.Moreover,the SBR response trends at P I 213.618 nm with all experimental parameters was strong in consistency with control-variable optimization results,which demonstrated the validity of the orthogonal array experimental design.This study established an efficient and accurate parameter optimization methodology for complex LIBS systems,significantly advancing the application of LIBS in environmental monitoring.

Objective:To assess the level of moral distress among pediatric nurses in China and explore its influencing factors, providing a reference for future interventions.Methods:A cross-sectional survey was conducted using a convenience sampling method from May 2022 to March 2023. Pediatric nurses meeting the inclusion and exclusion criteria were selected from children′s specialized hospitals, general hospitals, and maternal and child health hospitals across 16 provinces in China. Moral distress was assessed using the Chinese version of the Moral Distress Scale-Revised (MDS-R). Data analysis included descriptive statistics, non-parametric analysis, and multiple linear regression.Results:A total of 509 pediatric nurses participated in the survey, including 10 males and 499 females. Among them, 45 were aged ≤25 years, 268 were aged 26-35 years, 172 were aged 36-45 years, and 24 were aged >45 years.The median moral distress score was 58.00 (26.00, 77.50). Factors independently associated with higher levels of moral distress included having a master′s degree ( t = 2.33), working in a ward with more than 40 beds ( t = 3.38), working in a ward without parental accompaniment ( t = 2.60), being passively assigned to the nursing profession ( t = 2.63), and considering resignation but not leaving the job ( t = 3.85) (all P<0.05). Conclusions:Pediatric nurses in China experience a moderate level of moral distress. Further research is needed to understand its underlying causes and to develop preventive and intervention strategies.

OBJECTIVES: To evaluate whether adding Fuzheng Jiedu Xiaoji (FZJDXJ) therapy improves survival in advanced hepatitis B virus-related HCC (HBV-HCC) patients. METHODS: This prospective, randomized controlled study was performed at a major academic medical center in Beijing, China from October 2020 to October 2022. Eligible patients with advanced HBV-HCC were randomly divided equally (1:1) to receive either the combination of FZJDXJ and conventional Western medical therapy (63 cases, FZJDXJ group) or solely Western medicine (66 cases, control group). The study endpoints consisted of overall survival (OS) as the primary outcome, with progression-free survival (PFS), disease control rate (DCR), and adverse events (AEs) as secondary measures. RESULTS: The median OS was significantly prolonged in the FZJDXJ group at 8.9 months (95% CI: 6.0-11.9) vs. 4.4 months (95% CI: 3.2-7.3) in the control group (P<0.05). The hazard ratio for mortality in the FZJDXJ group was 0.59 (95% CI: 0.40-0.89), suggesting a 41% lower risk of death compared to the control group. The results revealed that patients receiving FZJDXJ therapy achieved a PFS of 5.1 months (95% CI: 4.1 to 7.2 months), compared to only 2.9 months (95% CI: 2.0 to 4.6 months) in the control group (P<0.05). Additionally, DCR was significantly elevated in the FZJDXJ group (20.6%) compared to the control group (10.6%, P<0.05). Subgroup analysis demonstrated that FZJDXJ significantly improved OS in patients with alpha-fetoprotein levels <400 ng/mL, age <60 years, Barcelona Clinic Liver Cancer (BCLC) stage C, and compensated liver function (Child-Pugh A and B, P<0.05). Multivariate analysis revealed that FZJDXJ therapy acted as an independent factor protecting against mortality within 1 year. Gastrointestinal symptoms are rare side effects, and no fatalities associated with the treatment were reported. CONCLUSION This randomized controlled trial demonstrated that FZJDXJ combined Western conventional therapy significantly improves OS and PFS in patients with advanced HBV-HCC. (registration No. ChiCTR2000033941).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/virology* ; Carcinoma, Hepatocellular/virology* ; Treatment Outcome ; Hepatitis B virus ; Adult ; Aged ; Hepatitis B/drug therapy*

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Aim To investigate the role of corylin in angiotensin Ⅱ(Ang Ⅱ)-induced cardiomyocyte hy-pertrophy and its underlying mechanisms.Methods An Ang Ⅱ-induced cardiomyocyte hypertrophy model was established and treated with corylin.Real-time PCR was employed to assess hypertrophic gene mRNA expression,and immunofluorescence was used to meas-ure cardiomyocyte surface area.Western blot and en-zyme activity assay kits were used to evaluate SIRT1 expression and activity.Results Corylin markedly mitigated Ang Ⅱ-induced hypertrophic gene expression and cardiomyocyte surface area enlargement.Moreo-ver,it prevented the Ang Ⅱ-mediated decline in SIRT1 protein levels and deacetylase activity.Further investi-gation indicated that corylin inhibited Ang Ⅱ-driven NF-κB transcriptional activity and the expression of its downstream target genes,such as TNF-α,IL-6,and IL-1β.Notably,SIRT1 silencing abolished the protective effects of corylin against cardiomyocyte hypertrophy,as well as its regulation of the SIRT1/NF-κB signaling pathway.Conclusion Corylin suppresses cardiomyo-cyte hypertrophy by modulating the SIRT1-dependent NF-κB signaling pathway.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

Objective:To observe the effect of combine treatment of butorphanol combined with esketamine in patients with remifentanil induced hyperalgesia after laparoscopic gynecological surgery.Methods:Based on randomized double-blind controlled trial,120 patients undergoing laparoscopic gynecological surgery in our hospital from April 2023 to October 2024 were divided into control group 1(received esketamine treatment,n=40),control group 2(received butorphanol treatment,n=40),and study group(received butorphanol combined with esketamine treatment,n=40).The awakening time,extubation time,mean arterial pressure(MAP),heart rate(HR),visual pain analog scale(VAS)score,ramsay sedation score,and incidence of adverse reactions among three groups were compared.Results:The awakening time and extubation time in the study group were shorter than those in the control group 1 and control group 2(P＜0.05).The MAP and HR in the study group were lower than those in the control group 1 and control group 2 at 30 minutes,60 minutes after extubation(P＜0.05).The VAS scores in the study group were lower than those in the control group 1 and control group 2 at 30 minutes,60 minutes after extubation(P＜0.05).The ramsay sedation scores in the study group were higher than those in the control group 1 and control group 2 at 30 minutes,60 minutes after extubation(P＜0.05).There was no significant difference in the incidence of postoperative adverse reactions among the three groups(P＞0.05).Conclusion:Butorphanol combined with esketamine can further alleviate remifentanil induced hyperalgesia after laparoscopic gynecological surgery,exert good sedative and analgesic effects,maintain hemodynamic stability,and have good safety.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.