The Proctor's reporting guideline for implementation strategies represents a landmark framework in the field of implementation science, aiming to address the issue of inconsistent reporting in implementation research by standardizing the naming, definition, and operationalization of implementation strategies, thereby enhancing the credibility and utility of research findings. This paper provides an in-depth interpretation of the core connotations of this reporting guideline and illustrates its application in developing interview outlines and specifying implementation strategies, using a brief smoking cessation intervention project as a case study. Through this reporting guideline, abstract recommendations for implementation are systematically transformed into clear, multidimensional operational guides, significantly improving the transparency of strategy connotations and the replicability of actual execution. Meanwhile, the case study highlights the flexibility of the guideline, which allows researchers to adapt the content and format of strategies based on local resources and cultural contexts, thus enhancing practical adaptability while maintaining scientific rigor. However, the application of Proctor's reporting guideline still faces challenges, primarily manifested in the potential confusion surrounding the constructs of temporality and dose in practice, as well as the challenges that the inherent flexibility of the guideline may pose to the assessment of fidelity and effectiveness. Despite these limitations, the reporting guideline remains a vital tool for implementation research; future efforts should focus on optimizing its application—through refining operational guidelines, standardizing flexible adaptations, and involving stakeholders—to better guide implementation studies and continuously promote high-quality development in the field.

ObjectiveBased on the clinical characteristics of chronic gouty arthritis （CGA） in both traditional Chinese and western medicine， this study aims to systematically evaluate the clinical concordance of existing CGA animal models， providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure， Wanfang， VIP Chinese Science and Technology Periodical Database （VIP）， and PubMed， all relevant literature on CGA animal models was collected. Based on the guidelines， the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes， and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction， high-protein diet induction （poultry lack urate oxidase）， and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature， the traditional Chinese and western medicine scoring data of each model were extracted， and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%， respectively. Among them， the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection， achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA， they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore， in the future， it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria， providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.

ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption （HSCD） on chronic gouty arthritis （CGA） rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated， using the random number table， to a normal group （n=8） and a model group （n =33）. CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate （250 mg·kg^-1·d^-1） and hypoxanthine （300 mg·kg^-1·d^-1）， combined with intra-articular injection of a monosodium urate （MSU） crystal suspension （50 μL， 25 g·L^-¹） into the left ankle twice weekly. After 4 weeks of modeling， 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group， an HSCD group （10.35 g·kg^-1·d^-1， gavage once daily）， an M1 polarization agonist group （L-methionine sulfoximine， 300 mg·kg^-1， subcutaneous injection every other day）， an M1 polarization agonist + HSCD group， an M2 polarization inhibitor group （PD0325901， 10 mg·kg^-1·d^-1， gavage once daily）， and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment， whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium （CMC-Na） vehicle （10.35 g·kg^-1·d^-1， gavage once daily）. All interventions were continued for four weeks. During the intervention period， except for the normal group， potassium oxonate （250 mg·kg⁻¹） and hypoxanthine （300 mg·kg^-1） were co-administered by gavage every other day to maintain the model. At the end of treatment， serum uric acid （SUA）， ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， chemokine C-C motif ligand 2 （CCL2）， S100 calcium-binding protein A8/A9 （S100A8/A9）， interleukin-10 （IL-10） and arginase-1 （Arg-1） in serum and joint fluid were determined by enzyme-linked immunosorbent assay （ELISA）. High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin （HE） staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase （iNOS） and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 （CD163） in synovial tissue. ResultsCompared with the normal group， the model group showed significantly elevated SUA level and joint swelling index， and increased levels of pro-inflammatory cytokines， CCL2， and S100A8/A9 in both serum and joint fluid （P<0.05）， accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated （P<0.05）. Compared with model group， rats in HSCD group had significantly lower SUA levels， attenuated joint swelling， reduced serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid， accompanied with alleviated MSU deposition and synovial inflammation （P<0.05）. HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS （P<0.05）， whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group， the M1 polarization agonist + HSCD group showed significantly reduced joint swelling， lower serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in joint fluid （P<0.05）. In addition， synovial inflammatory cell infiltration and angiogenesis were attenuated， and iNOS mRNA and protein expression levels were significantly reduced （P<0.05）. Compared with the M2 polarization inhibitor group， the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling， decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation （P<0.05）， whereas the levels of anti-inflammatory mediators （IL-10， Arg-1） and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats， at least in part， by inhibiting macrophage polarization toward the M1 phenotype.

Chronic heart failure （CHF） is a complex clinical syndrome caused by ventricular dysfunction， with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome， as the core pathogenesis of CHF， persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions， resulting in the accumulation of phlegm-fluid， blood stasis， and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention， forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang， the clinical experience of the traditional Chinese medicine （TCM） master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome， and achievements from molecular biological studies， this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild （Stage Ⅰ-Ⅱ）， severe （Stage Ⅲ）， and critical （Stage Ⅳ） stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical， pathophysiological， and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance， corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α（PGC-1α）/silent information regulator 2 homolog 1 （SIRT1） and ATPase activity. The severe stage centers on oxidative stress and structural damage， reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage， Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage， increase adenosine triphosphate （ATP） content， and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration， leading to the collapse of Yin-Yang equilibrium. At this stage， Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore （MPTP）， reduce cardiomyocyte apoptosis rate， and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF， this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.

Chinese patent medicines are the core preparations for disease prevention and treatment in clinical traditional Chinese medicine （TCM）. Their quality is the key to ensuring safe and effective medication and promoting the high-quality development of the TCM industry. At present， the quality evaluation of Chinese patent medicines faces prominent problems， such as inadequate control of quality consistency， over-reliance on single indicators， one-sided evaluation dimensions， unstable statistical methods， and poor implementability of research findings. These defects lead to insufficient scientificity of evaluation results， making it difficult to support the implementation of policies including centralized procurement， high quality， and favorable prices for Chinese patent medicines. According to the core requirements of quality evaluation for Chinese patent medicines， this study established a four-dimensional comprehensive evaluation system encompassing consistency index（CI）， content index（MI）， effect index（EI）， and preparation index（PI）. All evaluation indicators were normalized to achieve horizontal comparability. Meanwhile， an improved radar chart was introduced to realize the visualization of evaluation results. This method can systematically integrate four types of core quality attributes： Quality consistency， component content， biological activity， and preparation characteristics. It can effectively distinguish quality differences among products of the same specification from different manufacturers. The evaluation results are unique， stable， and not affected by the addition or reduction of samples， which takes scientificity， objectivity， and operability into account. This method can provide scientific and technical support for screening high-quality Chinese patent medicines and implementing policies of centralized procurement， high quality， and favorable prices. Moreover， it has important practical significance for improving the quality evaluation system of Chinese patent medicines and advancing the standard and modern development of TCM.

ObjectiveTo establish a comprehensive evaluation framework combining multi-component quantification with daily intake in response to the challenges posed by multiple coexisting dosage forms， single-faceted quality evaluation， and ambiguous clinical equivalence of Huoxiang Zhengqi preparations， and to compare the quality differences and superiority among eight commercially available dosage forms. MethodsA total of 75 batches of Huoxiang Zhengqi preparations from 25 manufacturers were investigated. Ultra-performance liquid chromatography-triple quadrupole-tandem mass spectrometry （UPLC-QqQ-MS/MS） coupled with gas chromatography-triple quadrupole-tandem mass spectrometry （GC-QqQ-MS/MS） was adopted to simultaneously quantify 20 core marker components. Normalization was performed based on equivalent raw herb concentrations to eliminate interferences from dosage forms， excipients， and specifications. Considering the specified clinical dosage， the actual daily intake level was calculated to comprehensively evaluate component retention， content uniformity， and potential differences in in vivo exposure among different dosage forms. ResultsThe quality of Huoxiang Zhengqi preparations differed greatly among dosage forms and manufacturers. On the basis of the recommended daily doses in the package inserts， the total daily intake of the 20 tested components ranged from 3.14 to 614.30 mg·d^-1， while that of hesperidin， a quality-control marker， ranged from 0.03 to 40.65 mg·d^-1. Atractylodin was detected only in tinctures and soft capsules， with concentrations ranging from （2.68±0.01） to （5.73±0.37） mg·L^-1. The soft capsules from manufacturer M22 had the highest atractylodin level， while atractylodin was not detected in the other dosage forms. Nucleosides were most abundant in the oral liquids and tinctures （M4 to M13）. The tincture from manufacturer M5 showed the highest nucleoside level of 29.12 mg·L^-1， whereas the granules had the lowest nucleoside levels， with that of M23 being only 3.48 mg·L^-1. Perillae Folium-related components varied greatly among batches， with an relative standard deviation （RSD） of 87.55%. The daily intake of hesperidin from all three granule products was below 3.6 mg·d^-1， the reference value calculated for Huoxiang Zhengqi Shui according to the 2025 edition of the Chinese Pharmacopoeia. ConclusionThe levels of active components differed significantly among different dosage forms of Huoxiang Zhengqi preparations. Tinctures contained more types and higher overall levels of active components， while soft capsules were better at preserving volatile components. Granules and dripping pills had lower overall levels of active components. The comprehensive evaluation method established in this study can provide a basis for the quality control， process optimization， and the selection of high-quality products.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

Objective:To explore the clinical efficacy of three different surgical timings of modified cervical cerclage in twin pregnant women with cervical insufficiency.Methods:The clinical data of 73 twin pregnant women who underwent modified cervical cerclage and had pregnancy outcomes in Qilu Hospital of Shandong University (Qingdao) from April 2014 to July 2023 were retrospectively analyzed. According to the different timings of surgery, they were divided into prophylactic cerclage group, ultrasound-indicated cerclage group (further divided into cervical length (CL)≤15 mm and 15 mm10 mg/L was a risk factor for preterm birth before 34 weeks of gestation ( OR=5.230, 95% CI: 1.616-16.929; P=0.006). Conclusions:In twin pregnant women with cervical insufficiency, prophylactic cerclage has the same surgical effect as ultrasound-indicated cerclage, while both prophylactic cerclage and ultrasound-indicated cerclage could significantly improve maternal and fetal outcomes compared with emergency cerclage. Twin pregnancies with CL≤15 mm might benefit from cervical cerclage. Postoperative CRP>10 mg/L is an independent risk factor for preterm birth before 34 weeks of gestation.

Objective:To investigate the dynamic characteristics of human papillomavirus (HPV) genomic integration during cervical lesion progression and the clinical value of HPV integration detection in stratify HPV-positive women, and to explore its molecular mechanisms in cervical carcinogenesis.Methods:A prospective cohort study was designed to enroll high-risk HPV (HR-HPV) positive women who underwent cervical cancer screening in Drum Tower Hospital Affiliated to Nanjing University Medical School and Nanjing Maternity and Child Health Care Hospital from July 2022 to July 2024. Cervical exfoliated cells samples were collected, and HPV whole genome targeted capture and high-throughput sequencing technology were used. The HPV integration patterns, host gene functional region distribution and pathway enrichment characteristics of 157 samples with different cervical lesions grades were analyzed, including 31 cases of normal cervix, 40 cases of cervical intraepithelial neoplasia (CIN) Ⅰ, 32 cases of CIN Ⅱ, 42 cases of CIN Ⅲ, and 12 cases of cervical cancer.Results:HR-HPV integration was detected in 80.2% (126/157) of the 157 HR-HPV positive samples. The incidence of HR-HPV integration in cervical cancer patients was 12/12, which was higher than that in normal women (77%, 24/31). The incidence of HPV16 integration was significantly higher in high-grade lesions, and the incidence of HPV16 integration was 43% (18/42) in CIN Ⅲ patients and 8/12 in cervical cancer patients ( P<0.001). A total of 14 438 integration events were detected in 126 samples with HPV integration. The integration sites were mainly distributed in the host intergenic region (51.0%, 7 359/14 438) and intronic region (38.1%, 5 494/14 438), and the integration frequency of viral L1 gene was the highest (28.4%, 4 498/16 781). Functional enrichment analysis showed that HPV integration-related host genes were significantly enriched in transport of small molecules,cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway, and purine ribonucleotide biosynthetic process, which synergistically drove carcinogenesis through multiple mechanisms. Conclusions:HPV integration events are significantly associated with the progression of cervical lesions. HPV integrated detection based on cervical exfoliated cells is expected to optimize the current screening strategy, reduce excessive intervention of HPV positive women and facilitate their accurate triage management.

Objective:To analyze the current status and trends in the clinical management and outcomes of respiratory distress syndrome (RDS) in preterm infants <32 weeks′ gestation admitted to the Chinese Neonatal Network (CHNN) from 2019 to 2023.Methods:A cross-sectional study was conducted from November 2024 to January 2025 using the CHNN cohort of very preterm and extremely preterm infants. A total of 30 869 RDS infants with gestational age <32 weeks were admitted within 1 day after birth to CHNN centers from 2019 to 2023. Data on demographics, perinatal management, early complications within 7 days of age, and in-hospital outcomes were collected. Yearly groups were defined by admission year. Trends by year were evaluated by Cochran-Armitage trend test, linear regression model and median regression model.Results:The gestational age at birth of 30 869 RDS infant was 28.9 (27.1, 30.7) weeks and the birth weight was 1 259 (932, 1 586) g. Males account for 56.5% (17 363/30 757). From 2019 to 2023, the prevalence of RDS was 73.8% (5 503/7 461), 74.5% (5 490/7 368), 79.8% (5 884/7 372), 81.6% (6 435/7 889), and 86.0% (7 557/8 789), respectively, showing an increasing trend year by year ( P<0.001). The overall rate of pulmonary surfactant administration was 72.4% (22 359/30 869), fluctuating between 71.2% (5 381/7 557) and 74.3% (4 089/5 503) over the 5-year period. Antenatal corticosteroids were administered to 82.3% (24 357/29 597) mothers of RDS infants and 23.6% (7 218/30 565) RDS infants received noninvasive positive end-expiratory pressure support in the delivery room, both showing a increasing trend over the 5 years (both P<0.001). The incidence of pneumothorax and the use rate of inhaled nitric oxide within 7 days of age were 1.3% (393/30 846) and 1.4% (436/30 869), respectively, both showing increasing trends over the 5 years (both P<0.001). The rate of complete course of antenatal corticosteroids administration was 64.6% (14 458/22 382), the rates of discharge against medical advice and mortality within 7 days of age were 5.3% (1 635/30 869) and 2.7% (724/26 803), respectively, all showing a decreasing trend over time (all P<0.05). Regarding in-hospital outcomes, mortality rate of RDS infants was 4.6% (1 228/26 803), showing a downward trend year by year ( P=0.005). The incidence of bronchopulmonary dysplasia (BPD) was 35.0% (9 417/26 919), and the combined incidence of death or BPD was 36.4% (9 763/26 803), both showing an increasing trend year by year (both P<0.001). Conclusions:RDS prevalence increased annually in preterm infants <32 weeks′ gestation from 2019 to 2023, with declining mortality but rising BPD rates. While antenatal steroid use and noninvasive positive end-expiratory pressure support application improved, full-course antenatal steroid compliance decreased. These findings highlight the need for standardized perinatal management protocols to improve the clinical management of RDS.