Objective To understand the epidemiological characteristics of a clustered outbreak of severe fever with thrombocytopenia syndrome(SFTS)as well as the ecological tick monitoring results for Zibo City, and to provide a scientific basis for formulating prevention and control strategies. Methods A case definition was cited before epidemic investigations were performed. Epidemiological investigations were performed on the index cases and their close contacts. Blood samples were collected from cases and close contacts, and quantitative real-time RT-PCR was used to detect SFTS virus(SFTSV)nucleic acid sequences. A retrospective cohort study was conducted to analyze risk factors and develop prevention and control strategies. Results This clustered outbreak involved two index cases and six close contacts with no deaths. Case A exhibited symptom onset on July 26. SFTS was confirmed on August 2. Case B exhibited symptom onset on August 1, and SFTS was confirmed on August 3. Patient B reported a recent history of tick bites. In both index cases, the incubation period for SFTS was inferred to be 7-12 days. The time interval from symptom onset to clinical diagnosis in the two cases ranged from 2-8 days, with an average period of 5 days. SFTSV nucleic acid test result were positive for both patients, whereas all six close contacts tested negative. All captured ticks tested negative for SFTSV using quantitative real-time RT-PCR. The densities of parasitic and free-living ticks in the emergency monitoring area around the cases were 12.60 and 4.65 ticks/(flag·100 m). In 2024, the average parasitic tick index and free-living tick density index were 4.21 and 2.43 ticks/(flag ·100 m)in Yiyuan County, respectively. Conclusions No evidence of human-to-human transmission was found in the assessed SFTS clusters. The infections were likely acquired through tick bites during fieldwork, and the risk of a subsequent outbreak spreading was low.

Objective To explore the independent risk factors for early failure of internal mammary artery grafts after coronary artery bypass grafting (CABG), and to construct and preliminarily evaluate a risk prediction model for the decline of internal mammary artery bridges, optimizing postoperative risk stratification and management strategies for patients. Methods Patients who underwent CABG at Fuwai Hospital, Chinese Academy of Medical Sciences from January 2016 to January 2020 were retrospectively enrolled. The primary endpoint was the failure of the internal mammary artery bridge one year after surgery, and the secondary endpoint was major adverse cardiac and cerebrovascular events (MACCE) within five years after surgery, including all-cause death, myocardial infarction, stroke, and revascularization. Patients were divided into a failure group and a non-failure group based on whether there was early failure of the internal mammary artery bridge after surgery. Independent risk factors for the failure of the internal mammary artery bridge were explored through the least absolute shrinkage and selection operator regression and multivariate logistic regression, and a failure risk prediction model was constructed and cross-validated. Patients were stratified for MACCE risk according to the total score of independent risk factors, and the 5-year cumulative MACCE-free rate was drawn using the Kaplan-Meier method. Results A total of 657 patients were included, among whom there were 54 patients in the failure group, including 38 males and 16 females, with an average age of (61.85±8.03) years; there were 603 patients in the non-failure group, including 467 males and 136 females, with an average age of (60.45±8.23) years. Multivariate logistic regression analysis showed that non-left main lesion [OR=3.28, 95%CI (1.41, 7.62), P=0.006], pulsatility index (PI)>3.0 [OR=2.63, 95%CI (1.20, 5.75), P=0.016], quantitative flow ratio (QFR)>0.80 [OR=5.57, 95%CI (2.98, 10.41), P<0.001] and in-hospital complications [OR=4.02, 95%CI (1.59, 10.19), P=0.003] were independent risk factors for the failure of internal mammary artery grafts after CABG. Compared with the prediction model in previous literature [area under receiver operating characteristic curve was 0.632, 95%CI (0.588, 0.688)], the risk prediction model constructed with QFR>0.80, PI>3.0, non-left main lesion and in-hospital complications had a higher predictive ability for early failure of internal mammary artery grafts [area under curve: 0.758, 95%CI (0.707, 0.817); net reclassification index: 0.272, 95%CI (0.180, 0.370); comprehensive discriminative improvement index: 0.109, 95%CI (0.059, 0.158); P<0.05]. The risk score of independent risk factors for internal mammary artery graft failure demonstrated significant MACCE risk stratification efficiency in the 5-year patient follow-up, with the high-risk group showing a significantly higher incidence of MACCE compared to the medium and low-risk groups (P=0.001). Conclusion QFR>0.80, PI>3.0, non-left main lesions, and in-hospital complications are independent risk factors for early failure of internal mammary artery grafts after CABG. The constructed risk prediction model based on this has preliminary capabilities in predicting the risk of internal mammary artery graft failure and MACCE risk stratification, which is beneficial for the postoperative management of CABG patients and improving their mid-long term prognosis.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Objective:To explore whether changes in the deltoid muscle tone of the affected side before and after arthroscopic rotator cuff repair (ARCR) are correlated with shoulder joint pain and shoulder joint function.Methods:A total of 55 patients (22 males and 33 females, aged 60.44±9.54 years with a range of 41 to 78 years, BMI 25.86±4.25 kg/m 2 with a range of 18.82 to 42.32 kg/m 2, symptom duration 5.94±7.27 months with a range of 0.3 to 36.0 months) diagnosed with rotator cuff tear and underwent ARCR at the First Affiliated Hospital of Tsinghua University between December 2019 and June 2023 were included. All the patients suffered from unilateral symptom (23 left side and 32 right side), the size of rotator cuff tear was 16.47±5.98 mm (range, 6.92-36.38 mm). Following the operation, postoperative rehabilitation exercises were arranged with a minimum follow-up duration of six months. The muscle tone of the deltoid was measured bilaterally using a muscle tone tester before the operation and at 1, 3, 6 months after operation. The area under curve (AUC) of the pressure-displacement curve was used to reflect the muscle tone, with larger AUC values represent less muscle tone. Visual analogue scale (VAS) and Constant-Murley score were evaluated and recorded at the same time points. Results:At 1, 3, and 6 months postoperatively, the VAS scores were all significantly reduced compared to preoperative values, with the Constant-Murley scores and the AUC values of the pressure-displacement of the affected-side deltoid significantly increased ( P<0.05). The postoperative AUC values of the pressure-displacement of the affected side deltoid muscle were significantly lower than those of the contralateral side ( P<0.05). There was no significant correlation between the changes in deltoid muscle pressure-displacement AUC and age, gender, disease duration, or BMI ( P>0.05), while a significant positive correlation was observed between the AUC and the size of the rotator cuff tear ( r=0.369, P=0.006). There was a positive correlation between the change in VAS and the change in deltoid muscle pressure-displacement AUC ( t=0.424, P<0.001), and the unary linear regression equation was: change in VAS=4.314+0.837×(change in deltoid muscle pressure-displacement AUC). There was a positive correlation between the changes in Constant-Murley shoulder score and the changes in deltoid AUC ( t=5.336, P<0.001), and the unary linear regression equation was: change in Constant-Murley score=24.838+6.097×(change in deltoid muscle pressure-displacement AUC). Conclusions:ARCR can reduce the affected side deltoid muscle tone, relieve shoulder pain and improve shoulder joint function. The changes in deltoid muscle tone are positively correlated with the degree of shoulder pain and function.

Apurinic/apyrimidinic endonuclease 1(APE 1)is a multifunctional protein that plays important roles in DNA repair and regulation of gene expression.Because APE 1 is overexpressed in various cancers,it can serve as a cancer biomarker for aiding clinical diagnosis,guiding therapy,and monitoring prognosis.On this basis,a label-free fluorescent probe was designed based on the primer exchange reaction(PER)strategy for highly sensitive detection of APE 1 activity.In the absence of APE 1,the structure of catalytic hairpin(HP)was stable and could not form G-quadruplex.Therefore,the background fluorescence of this sensing system was very low due to the dissociation of thioflavin T(ThT).In the presence of APE 1,the apurinic/apyrimidinic(AP)site of HP was cleaved by APE 1 and a short nucleic acid fragment that acted as a primer to initiate PER was generated.After PER reaction,a large number of G-quadruplex were produced,which could specifically bind with ThT and resulted in significant increase of fluorescence signal.The combination of low background design of HP and PER amplification made this biosensor had high sensitivity with a detection limit(3σ)of 0.0008 U/mL.Furthermore,the primer sequence was directly generated by the cleavage of APE 1 without additional addition,which not only increased the specificity of the reaction,but also simplified the experiment procedure.Moreover,the use of label-free fluorescence signal reduced the cost of the experiment,and realized rapid detection of APE 1.Finally,this sensor was used to detect APE 1 in human serum samples with spiked recoveries of 91%-104%,proving great potential in study of biological enzyme.

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

Five meroterpenoids, rhodonoids K-M (1-2), daurichromene E (3), and grifolins A-B (4-5), together with seven known compounds (6-12), were isolated from Rhododendron anthopogonoides. The chemical structures of these compounds were elucidated through comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), ultraviolet (UV), infrared spectroscopy (IR), and nuclear magnetic resonance (NMR) data. Their absolute configurations were determined by comparing experimental electronic circular dichroism (ECD) spectra with computed values. Notably, compounds 1 and 3 demonstrated significant inhibitory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. These compounds markedly suppressed the mRNA expressions of inflammatory factors, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) while also down-regulating the protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2).
Mice ; Rhododendron/chemistry* ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Terpenes/isolation & purification* ; Molecular Structure ; Tumor Necrosis Factor-alpha/immunology* ; Cyclooxygenase 2/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Macrophages/immunology* ; Interleukin-6/immunology* ; Lipopolysaccharides ; Interleukin-1beta/immunology*