ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.

Purpose To develop a nomogram combined radiomics,clinical and CT morphographic features for the prediction of the acquired T790M mutation in patients with advanced non-small cell lung cancer with resistance after the duration of first-line epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI)treatment.Materials and Methods The chest CT images and clinical data of 116 patients who underwent secondary biopsy after disease progression during first-line TKI treatment for advanced non-small cell lung cancer with EGFR sensitive mutations,from December 2016 to December 2022 in Shaoxing People's Hospital were retrospectively analyzed.All patients were randomly divided into a training cohort(n=81)and a validation cohort(n=35),at a ratio of 7︰3.The regions of interest of the lesion were delineated,and radiomics features were extracted.Feature selection was performed via the maximum relevance minimum redundancy and the least absolute shrinkage and selection operator methods.Clinical features were selected via univariate and multivariate Logistic regression.A nomogram combined clinical and radiomics features was subsequently constructed.The predictive ability of the combined model was evaluated via receiver operator characteristic curve,calibration curves and decision curve analysis.Results The progression-free survival of first-line EGFR-TKIs(OR=1.086,P=0.041),initial EGFR profile(OR=0.280,P=0.021),vascular convergence(OR=4.050,P=0.036)and air bronchogram(OR=3.265,P=0.030)were highly correlated with the acquired T790M mutation.The combined model demonstrated good predictive performance for acquired T790M mutation,both in the training set(AUC=0.867,95%CI 0.790-0.944)and the validation set(AUC=0.895,95%CI 0.786-1.000).The calibration curve showed good calibration power,and the decision curve analysis demonstrated a significant net benefit.Conclusion A radiomics-clinical nomogram based on CT radiomics has the potential to predict acquired T790M mutation and could be a complementary tool for T790M mutation detection after resistance to first-or second-generation EGFR-TKIs.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective To investigate the short-term efficacy of 3D-printed artificial vertebral body combined with PEEK-Cage implantation in anterior cervical surgery for ossification of the posterior longitudinal ligament of the cervical spine(OPLL).Methods The clinical data of 15 patients with OPLL who underwent anterior cervical surgery with 3D-printed artificial vertebral body and PEEK-Cage implantation in the Fifth Department of Orthopaedics,Liaoning Provincial People's Hospital from September 2022 to June 2023 was retrospectively analyzed.The surgical time,intraoperative blood loss,postoperative drainage volume,bed rest time,hospital stay,and surgery-related complications of patients were analyzed.The Japanese Orthopaedic Association(JOA)score and visual analogue scale(VAS)score of patients were counted before surgery,3 days after surgery,1 month after surgery and 6 months after surgery.The changes of Cobb angle of fusion segment of patients were recorded before surgery,3 days after surgery,1 month after surgery and 6 months after surgery.Results All 15 patients successfully completed the surgery.The surgical time was 130 to 160 minutes,with an average of(148.68±10.04)minutes.The intraoperative blood loss was 50 to 200 mL,with an average of(130.0±18.8)mL.The postoperative drainage volume was 220 to 980 mL,with an average of(270.0±24.6)mL.The bed rest time was 3 to 11 days,with an average of(3.6±2.8)days.The hospital stay was 7 to 16 days,with an average of(8.2±2.6)days.All patients'incisions healed in the first stage,and no infection occurred.One patient suffered from dural sac tear during surgery;4 patients had dysphagia after surgery;1 patient suffered from muscle weakness of one limb after surgery;Hematoma formed in the incision of cervical spine in 1 patient 3 days after surgery.At 3 days,1 month,and 6 months after surgery,the Cobb angle,VAS score and JOA score of 3 patients with myeloid symptoms and upper limb root pain were significantly improved compared with those before surgery(P<0.05),and the Cobb angle and JOA score of 12 patients with only myeloid symptoms were significantly improved compared with those before surgery(P<0.05).Conclusion 3D-printed artificial vertebral body combined with PEEK-Cage implantation in anterior cervical surgery is an effective method for the treatment of OPLL,which can significantly relieve patients'pain and improve their dysfunction in a short time,with good stability and fusion effect.

Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnor-malities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms under-lying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Uti-lizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expres-sion QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4 110,NControls=13 569),we imple-mented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Associa-tion Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD patho-genesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate＜0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were asso-ciated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were asso-ciated with CJD at the transcriptional level.

Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.

Objective To investigate the short-term efficacy of transforaminal endoscope combined with percutaneous fixation in the treatment of single-segment Brucella spondylitis with intraspinal abscess. Methods The clinical data of 14 patients with single-segment lumbar Brucella spondylitis with intraspinal abscess treated by transforaminal endoscopic decompression combined with percutaneous fixation in our hospital from March 2021 to August 2022 were retrospectively analyzed. The operation time,intraoperative blood loss,erythrocyte sedimen-tation rate(ESR) and C-reactive protein(CRP) before operation,3 days and 3 months after operation,postoperative drainage volume,post-operative bed rest time and occurrence of complications were recorded. Before operation,3 days and 3 months after operation,the visual analogue scale (VAS) was used to evaluate the pain degree of lower back and leg,the lumbar function was evaluated by Japanese Orthopaedic Association (JOA) score,Oswestry disability index (ODI)was used to evaluate the dysfunction,and the modified Macnab criteria was used to evaluate the good to excellent rate of efficacy. Results The operation time of 14 patients was 182～217 min,with an average of (197.3±18.6) minutes. The mean intraoperative blood loss was (37.8±15.5)mL;the mean drainage volume was (23.5±5.8)mL;the postoperative bed rest time was (3.5±1.4) days. ESR and CRP gradually decreased 3 days and 3 months after operation compared with those before opera-tion,with statistically significant differences(P<0.05). The VAS scores of lower back and legs,JOA scores,and ODI at each time point of follow-up after operation were significantly improved compared with those before operation,with statistically significant differences (P<0.05). After 3 months of follow-up,the good to excellent rate of efficacy was 85.7％.Conclusion The minimally invasive technique of transforaminal endoscope in the treatment of Brucella spondylitis with intraspinal abscess can conduct neuraxial root decompression,abscess removal,and local surgical area irrigation,significantly relieve the pain of lower limbs,and combined with the percutaneous fixation can significantly alleviate the low back pain and improve the function of patients. The combination of the two methods is minimally invasive,safe and effective in the treatment of Brucella spondylitis with intraspinal abscess.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

OBJECTIVE: As an age-related neurodegenerative disease, the prevalence of mild cognitive impairment (MCI) increases with age. Within the framework of traditional Chinese medicine, spleen-kidney deficiency syndrome (SKDS) is recognized as the most frequent MCI subtype. Due to the covert and gradual onset of MCI, in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes. There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS (MCI-SKDS). METHODS: This investigation enrolled 312 elderly individuals diagnosed with MCI, who were randomly distributed into training and test datasets at a 3:1 ratio. Five machine learning methods, including logistic regression (LR), decision tree (DT), naive Bayes (NB), support vector machine (SVM), and gradient boosting (GB), were used to build a diagnostic prediction model for MCI-SKDS. Accuracy, sensitivity, specificity, precision, F1 score, and area under the curve were used to evaluate model performance. Furthermore, the clinical applicability of the model was evaluated through decision curve analysis (DCA). RESULTS: The accuracy, precision, specificity and F1 score of the DT model performed best in the training set (test set), with scores of 0.904 (0.845), 0.875 (0.795), 0.973 (0.875) and 0.973 (0.875). The sensitivity of the training set (test set) of the SVM model performed best among the five models with a score of 0.865 (0.821). The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset. The DCA of all models showed good clinical application value. The study identified ten indicators that were significant predictors of MCI-SKDS. CONCLUSION The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical; the model demonstrates good predictive value and clinical applicability, and the DT model had the best performance. Please cite this article as: Ai YT, Zhou S, Wang M, Zheng TY, Hu H, Wang YC, Li YC, Wang XT, Zhou PJ. Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly. J Integr Med. 2025; 23(4): 390-397.
Humans ; Cognitive Dysfunction/diagnosis* ; Aged ; Male ; Female ; Machine Learning ; Spleen ; Aged, 80 and over ; Kidney ; Medicine, Chinese Traditional

BACKGROUND: Electroacupuncture (EA) may affect the severity of hot flashes (HFs) associated with natural menopause and provide additional benefits for postmenopausal women. However, the evidence for its effectiveness in the management of early postmenopausal HFs remains inadequately understood. OBJECTIVE: We designed this trial to assess the efficacy and safety of EA for relieving early postmenopausal HFs. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This randomized sham-controlled trial involved 72 women with HFs. The participants were divided equally into the intervention and control groups. The intervention group was treated with EA, while the control group was treated with sham acupuncture. The main acupoints used were Hegu (LI4), Guanyuan (RN4), Sanyinjiao (SP6), Taixi (KI3), Fuliu (KI7) and Shenshu (BL23). All participants received 18 treatment sessions, distributed across a 6-week period. The treatment was administered on three occasions per week, adhering to a fixed weekday schedule (Monday, Wednesday, Friday or Tuesday, Thursday, Saturday) with a minimum interval of one day between sessions. Each patient received a 12-week follow-up. MAIN OUTCOME MEASURES: The HF score was the primary outcome. Participants documented the frequency and severity of HFs in a 7-day symptom diary, which provided data for calculating the HF score. Secondary outcomes were the Menopause Rating Scale (MRS), Menopause-Specific Quality of Life Questionnaire (MENQOL), Pittsburgh Sleep Quality Index (PSQI) and Traditional Chinese Medicine Syndrome Score Scale (TCMSSS), as well as estradiol (E₂), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. RESULTS: Both groups demonstrated significant reductions in HF scores after the treatment and during the follow-up (P < 0.001). Immediately after completion of the 6-week treatment cycle and at 12 weeks post-intervention, the HF scores were similar in both groups. At week 6, the intervention group showed significantly greater improvements in MRS, MENQOL (vasomotor, psychosocial, and physical), PSQI and TCMSSS scores (P < 0.05). The improvements in the MENQOL (vasomotor, and psychosocial) and PSQI total scores persisted through the follow-up (P < 0.05). However, the results showed no significant inter- or intragroup differences in sexual scores on the MENQOL (P > 0.05). EA did not significantly decrease E₂, LH or FSH levels compared to placebo. The incidence of adverse events was similar in both groups. CONCLUSION: EA does not significantly improve HFs in early postmenopausal patients. However, it enhances the quality of sleep and decreases menopausal symptoms across vasomotor, psychosocial and physical domains. TRIAL REGISTRATION Chinese Clinical Trial Registry (http://www.chictr.org.cn); Trial ID: ChiCTR2300072002. Please cite this article as: Wang HX, Yu XT, Hu J, Chen JJ, Mei YT, Chen YF. Electroacupuncture for hot flashes in early menopause: A randomized sham-controlled trial. J Integr Med. 2025; 23(5):519-527.
Humans ; Female ; Electroacupuncture ; Hot Flashes/therapy* ; Middle Aged ; Acupuncture Points ; Quality of Life ; Menopause ; Treatment Outcome ; Adult