ObjectiveTo investigate the protective effect and mechanism of Wendan Ningxin granules （WNG） on susceptibility to atrial fibrillation （AF） in mice with inflammatory injury. Methods100 C57BL/6 mice were divided into a blank control group， a model group， a low-dose WNG group （2.34 g·kg^-1·d^-1）， a high-dose WNG group （4.68 g·kg^-1·d^-1）， and an amiodarone positive control group （0.091 g·kg^-1·d^-1）， with 20 mice in each group. Except for the blank control group， mice in other groups received intraperitoneal injections of lipopolysaccharide （LPS） to establish an inflammatory injury model. Treatment groups received continuous intragastric administration of their respective interventions for four weeks. During the fourth week， the treatment groups received LPS injections concurrently with their treatments. The blank control and model groups received distilled water （10 mL·kg^-1·d^-1） by gavage， with a gavage volume of 10 mL·kg^-1 for all groups， once daily. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe atrial tissue morphology and fibrosis degree. Immunohistochemistry was used to assess the expression of α-smooth muscle actin （α-SMA） in mouse atrial tissue. Electrophysiological detection was performed using a multi-channel electrophysiology mapping system to measure AF inducibility， AF duration， and atrial effective refractory period （AERP）. High-resolution optical mapping was used to measure action potential duration （APD） dispersion， conduction heterogeneity index， and calcium transient （CaT） dispersion. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of proteins related to diastolic calcium leakage in mouse atria： Ca²⁺/calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）， ryanodine receptor 2（RyR2）， sarco/endoplasmic reticulum Ca²⁺-ATPase （SERCA）， and sodium-calcium exchanger （NCX）. Western blot analysis was performed to detect the expression of CaMKII， RyR2， SERCA， and NCX proteins in myocardial tissue from each group. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of inflammatory factors interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）. ResultsPathological staining results showed that compared with the blank control group， the model group exhibited disrupted atrial tissue structure， inflammatory cell infiltration， atrial fibrosis， and diffuse infiltration of numerous brown α-SMA positive cells in the atrial interstitium （P<0.01）. AF could be induced by electrical stimulation with a longer duration. AERP was shortened， while APD dispersion， conduction heterogeneity index， and CaT dispersion were increased （P<0.01）. The expression of proteins associated with diastolic calcium leakage， including CaMKⅡ， RyR2， and NCX1， showed elevated mRNA and protein levels， whereas SERCA2a mRNA and protein expression decreased （P<0.05）. Serum levels of inflammatory factors IL-1β and TNF-α were elevated （P<0.01）. Compared with the model group， intervention with WNG alleviated cardiac structural damage， reduced inflammatory cell infiltration， improved atrial fibrosis， and reduced the diffuse infiltration of α-SMA positive cells （P<0.01）. AF inducibility and AF duration upon electrical stimulation were significantly reduced （P<0.05）， AERP was prolonged （P<0.05）， mRNA and protein expression of CaMKⅡ， RyR2， and NCX1-proteins associated with diastolic calcium leakage-were reduced， whilst mRNA and protein expression of SERCA2a increased （P<0.05）， and serum levels of IL-1β and TNF-α were decreased （P<0.01）. ConclusionBoth low‑ and high‑dose WNG can effectively reduce susceptibility to inflammation-related AF. The mechanism by which WNG reduce AF susceptibility may be related to regulating proteins involved in sarcoplasmic reticulum diastolic calcium leak， thereby improving cardiac electrical remodeling， and alleviating inflammation-induced myocardial fibrosis， thus improving cardiac structural remodeling.

Objective To explore the functional impact of A-to-I editing in the seed region of miR-411 during post-myocardial infarction (MI) fibrosis and elucidate its therapeutic potential. Methods Integrating GEO database with myocardial RNA-seq data from MI mouse models, we identified dynamic A-to-I RNA editing in small noncoding RNAs across MI progression (1 day to 8 weeks post-MI). Four miRNAs exhibited differential editing rates between MI and controls, with miR-411 showing progressive editing enhancement at seed region position 4 (P＜0.01). This editing event was validated in both murine MI models and human heart failure specimens. Results The A-to-I editing ratio change of the 4th nucleotide in the seed region of miR-411 mainly occurs in cardiac fibroblasts rather than cardiomyocytes, and the editing at this site depends on ADAR2 rather than ADAR1. Edited miR-411 (ED-miR-411) diverged from wild-type miR-411 (WT-miR-411) in suppressing collagen-related pathways (extracellular matrix [ECM]-receptor interaction, collagen-containing ECM, ECM organization; P＜0.01) in cardiac fibroblasts. Mechanistically, dual-luciferase assays confirmed ED-miR-411 directly targeted the 3′UTR and suppressed expression of type Ⅱ transforming growth factor (TGF)-beta receptor (TGFBR2) and CD44, which were key drivers of TGF-β-mediated fibroblast activation. ED-miR-411 overexpression blunted TGF-β-induced collagen synthesis and myofibroblast proliferation (P＜0.05). In vivo, intramyocardial delivery of ED-miR-411 mimics at 1 week post-MI reduced fibrosis by 40% and improved ejection fraction by 15% (P＜0.01 vs controls), whereas WT-miR-411 showed no therapeutic effect. Conclusions A-to-I editing of miR-411 emerges as an endogenous anti-fibrotic mechanism by repressing TGFBR2 and CD44, thereby disrupting TGF-β signaling and ECM dysregulation. Our findings highlight ED-miR-411 as a novel RNA-based therapeutic candidate to mitigate post-infarction cardiac remodeling.

A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

Background/Aims: The pathophysiology of refractory gastroesophageal reflux disease (RGERD), which differs from proton pump inhibitor dependent gastroesophageal reflux disease (DGERD), remains incompletely elucidated. This study aims to compare esophageal motility patterns, transdiaphragmatic pressure gradients (TPG), and reflux profiles between RGERD and DGERD patients, and to delineate dynamic pressure gradient-esophagogastric junction (EGJ) interactions in these patients. Methods: In this retrospective study, 274 patients who underwent 24-hour impedance-pH monitoring and high-resolution manometry, along with an assessment of proton pump inhibitor responsiveness, were classified as RGERD (32.5%), DGERD (54.4%), or non-GERD (13.1%). Clinical characteristics, TPG, esophageal motility, and reflux metrics were compared between RGERD and DGERD patients. Subgroup analysis excluding hiatal hernia (HH) was conducted to investigate the pathophysiology of RGERD. Results: The RGERD group exhibited a significantly higher proportion of chest pain compared to the DGERD group. Regarding reflux profiles, RGERD patients without HH (RGERDHH- group) experienced increased weakly acidic reflux (P < 0.001) and prolonged bolus exposure (P = 0.006) compared to their counterparts (DGERDHH- group). Mechanistically, the RGERDHH- group showed reduced lower esophageal sphincter basal pressure (P = 0.010) and EGJ contractile integral (P = 0.005). Notably, following a wet-swallow, the RGERDHH- group experienced the significant elevation in gastric pressure and TPG. Correlation analyses revealed weakly acidic reflux and bolus exposure were positively correlated with gastric pressure variation, and inversely correlated with lower esophageal sphincter basal pressure. Conclusions Transient gastric pressure elevation and compromised EGJ barrier function drive weakly acidic reflux and esophageal bolus exposure. This pressure gradient-barrier mismatch underpins the refractoriness of RGERD.

ObjectiveTo investigate the therapeutic effects of modified Baoyuantang combined with Linggui Zhugantang on post-myocardial infarction heart failure in rats and its influence on NOD-like receptor pyrin domain-containing protein 3 （NLRP3）/gasdermin D （GSDMD）-mediated pyroptosis. MethodsSixty male SD rats were randomized into sham， model， low-， medium-， and high-dose （2.52， 5.04， 10.08 g·kg^-1， respectively） modified Baoyuantang combined with Linggui Zhugantang， and sacubitril/valsartan sodium （0.021 g·kg^-1） groups， with 10 rats in each group. Except the sham group， the other groups underwent left anterior descending coronary artery ligation for the modeling of myocardial infarction. The treatment groups were administrated with corresponding drugs by gavage， and the sham and model groups received an equal volume of normal saline. Administration began on the first day after successful modeling， once daily， for 4 weeks. Echocardiography was used to measure left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic and end-systolic diameters （LVIDd and LVIDs）， left ventricular posterior wall thicknesses at end-diastole and end-systole （LVPWd， LVPWs）， and left ventricular volumes at end-diastole and end-systole （LV Vold and LV Vols）. Cardiac mass index and heart weight-to-tibia length ratio were calculated. Hematoxylin-eosin （HE） staining and Sirius Red staining were performed to observe myocardial morphology and collagen deposition. Immunohistochemistry was employed to detect the expression of type I collagen （Collagen Ⅰ）， NLRP3， GSDMD， and interleukin-1β （IL-1β）. Transmission electron microscopy was used to observe the mitochondrial ultrastructure. Tetramethylrhodamine methyl ester （TMRM） staining was conducted to assess mitochondrial membrane potential （MMP） in cardiomyocytes. Real-time PCR was used to quantify the mRNA levels of NLRP3， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， IL-1β， GSDMD， and interleukin-18 （IL-18） in the myocardial tissue. Western blotting was employed to determine the protein levels of NLRP3， Caspase-1， GSDMD， IL-1β， IL-18， nuclear factor kappa-B （NF-κB） p50， and NF-κB p65 in the myocardial tissue. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the serum levels of tumor necrosis factor-α （TNF-α）， IL-1β， and IL-6. ResultsCompared with the sham group， the model group showed increased LVIDd， LVIDs， LV Vold， LV Vols， cardiac mass index， and heart weight-to-tibia length ratio （P<0.05）， decreased LVPWs， LVEF， LVFS， and MMP （P<0.05）， evident myocardial inflammation， fibrosis， and mitochondrial damage， upregulated expression of NLRP3， Caspase-1， GSDMD， IL-1β， IL-18， NF-κB p50， and NF-κB p65， and elevated serum levels of TNF-α， IL-1β， and IL-6 （P<0.05）. Compared with the model group， modified Baoyuantang combined with Linggui Zhugantang reduced the LVIDd， LVIDs， LV Vols， cardiac mass index， and heart weight-to-tibia length ratio （P<0.05）， increased the LVPWs， LVEF， LVFS， and MMP （P<0.05）， alleviated myocardial inflammation and fibrosis， improved the mitochondrial structure and function， downregulated the expression of NLRP3， Caspase-1， GSDMD， IL-1β， IL-18， NF-κB p50， and NF-κB p65 （P<0.05）， and reduced the serum levels of TNF-α， IL-1β， and IL-6 （P<0.05）. ConclusionModified Baoyuantang combined with Linggui Zhugantang can ameliorate post-myocardial infarction ventricular remodeling and improve the cardiac function by reducing mitochondrial damage and inhibiting NLRP3/GSDMD-mediated pyroptosis.

ObjectiveTo determine the effects of tuina at "Weizhong （BL 40）" on mechanical pain hypersensitivity in a rat model of chronic dorsal root ganglion （CCD）， and to preliminarily explore the anatomical distribution characteristics of neural afferents associated with "Weizhong （BL 40）" acupoint and their central projections. MethodsThirty SD rats were randomly assigned to a sham operation group， a model group， and a tuina group， with 10 rats in each group. In the model group and the tuina group， a chronic compression of CCD model was established by implanting stainless-steel rods into the right L4/5 and L3/4 intervertebral foramina. Rats in the sham operation group underwent surgical exposure only. From day 4 to day 28 after modeling， rats in the tuina group received daily manipulation at the right "Weizhong （BL 40）" （pressure： 5 N； frequency： 2 Hz； duration： 10 min/session）. Rats in the sham operation group and the model group were subjected only to fixation. Mechanical withdrawal threshold （MWT） was assessed before modeling and on day 3， 7， 14， 21， and 28 after modeling. On day 29 after modeling， pseudorabies virus （PRV）， a retrograde trans-multisynaptic tracer， was injected into the right "Weizhong （BL 40）" acupoint in rats from the model group. After 120 h， rats were perfusion-fixed through the heart， and local tissues surrounding the "Weizhong （BL 40）" acupoint， corresponding lumbar dorsal root ganglia， lumbar spinal cord， and brain tissues were collected for fluorescence imaging of PRV-positive signals. ResultsCompared to the sham operation group， rats in the model group and the tuina group showed significantly reduced MWT on day 3， 7， 14， 21， and 28 after modeling （P＜0.05）. Compared to the model group， rats in the tuina group exhibited significantly increased MWT on day 21 and 28 after modeling （P＜0.05）. Fluorescence imaging revealed PRV-positive signals in the deep fascial layer of local muscle tissue at "Weizhong （BL 40）"， the L4 and L5 dorsal root ganglia， the dorsal horn and central canal region of the spinal cord， as well as the primary somatosensory cortex （S1）， secondary motor cortex （M2）， and anterior cingulate cortex （ACC）. Among the examined cortical regions， M2 contained the largest number of PRV-positive neurons. ConclusionTuina at "Weizhong （BL 40）" alleviates mechanical hyperalgesia in rats with the chronic compression of CCD model. A traceable neuroanatomical connection exists between the linking deep tissues within "Weizhong （BL 40）" region and the corresponding lumbar dorsal root ganglia， the spinal dorsal horn， and specific cortical areas.

Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease closely related to metabolism， which is mainly characterized by abnormal lipid deposition in hepatocytes. In recent years， with the increasing prevalence of obesity and metabolic syndrome， NAFLD has become one of the most common chronic diseases in the world. The pathogenesis of NAFLD is complex and varied， involving the cross-regulation of multiple signaling pathways such as glucose-lipid metabolism， oxidative stress， and inflammation. The TLR4 signaling pathway plays a key role in the development and progression of NAFLD， and abnormal activation of this pathway accelerates the deterioration of NAFLD by promoting the release of pro-inflammatory cytokines， inducing oxidative stress， and exacerbating insulin resistance. Studies have shown that traditional Chinese medicine （TCM） can regulate the TLR4 signaling pathway to alleviate the symptoms and pathological features of NAFLD. The present review summarizes the experimental research progress in the TCM regulation of the TLR4 signaling pathway in treating NAFLD in the past 5 years， covering a wide range of TCM active ingredients （such as polysaccharides， terpenoids， alkaloids， flavonoids） and compound prescriptions. The active ingredients and compound prescriptions of TCM can effectively ameliorate lipid metabolism disorders， reduce insulin resistance， regulate intestinal flora， and inhibit inflammation and oxidative stress by regulating the TLR4 signaling pathway via multiple targets and pathways， thus slowing down the progression of NAFLD. Through in-depth analysis of the pathological mechanisms of NAFLD and exploration of the potential of TLR4 signaling pathway as a therapeutic target， we can provide theoretical support for the application of TCM in the treatment of NAFLD， as well as new perspectives and directions for future clinical research and new drug development， thereby promoting the innovation and development of therapeutic strategies for NAFLD.

OBJECTIVE To provide a reference for revising the safety content of traditional Chinese medicine（TCM） instructions. METHODS A systematic analysis was conducted on the relevant announcements on the revision of TCM instruction from 2013 to 2024， including the year of publication， drug name， drug formulation， announcement release time， and the average number of revisions made to three safety contents （contraindication， adverse drug reaction， and precaution）. According to the report data of national adverse drug reaction monitoring from 2013 to 2024， analyze the proportion of TCM in all adverse drug reactions， the composition ratio of adverse drug reaction of different dosage forms of drugs [TCM injection， oral TCM， other （topical） TCM]. RESULTS From 2013 to 2024， the National Medical Products Administration issued a total of 101 notices on the revision of TCM instruction， involving 241 types of TCM. Among them， there were 163 types of oral TCM， 25 types of TCM injection， and 53 types of other （topical） TCM. There were 3， 10 and 0 types of TCM injection， oral TCM， and other （topical） TCM with missing safety content， respectively. The main source of adverse drug reaction data for TCM injections was post- marketing monitoring data （accounting for 48.00%）； the main source of adverse drug reaction data for oral TCM was monitoring data （accounting for 71.17%）； 73.58% of other （topical） TCM did not mention the source of adverse drug reaction data. The report on national adverse drug reaction monitoring showed that the proportion of all adverse drug reactions of TCM had decreased from 17.3% in 2013 to 12.1% in 2024. Among them， the proportion of adverse drug reaction of TCM injection in the three dosage forms of TCM had decreased from 61.3% in 2015 to 24.6% in 2024， while the proportion of adverse drug reaction of oral TCM in the three dosage forms of TCM had increased from 34.7% in 2015 to 64.0% in 2024. CONCLUSIONS The risk management of TCM safety content has achieved results in China， but still faces three major challenges： strongdependence on passive monitoring， insufficient data traceability， and missing key content. It is urgent to improve safety content by dosage form， optimize data sources， and fully utilize real-world evidence to supplement safety content.

Reporting guidelines are structured checklists for researchers to follow when reporting spe-cific types of studies.As researches conducted in real-world settings to address practical issues,implementa-tion research has stringent requirements for the replicability of result and the transparency of reporting,making its reporting guidelines particularly important.This paper systematically introduces the reporting guidelines in the field of implementation science,outlines their classification systems and scopes of applica-tion,and focuses on explaining the core characteristics and functions of five key reporting guidelines,inclu-ding the Standards for Reporting Implementation Studies(StaRI),Reporting guidelines for implementation and operational research,the Template for Intervention Description and Replication(TIDieR),the Frame-work for Reporting Adaptations and Modifications-Enhanced(FRAME),and recommendations for specifying and reporting implementation strategies.Furthermore,combined with the PEDALs research paradigm in im-plementation science,this paper further clarifies the specific application pathways for reporting guidelines and discusses directions for refinement,aiming to provide references for researchers to select appropriate reporting guidelines.

Objective:To explore the effects of age and gender on the sagittal spinal-pelvic parameters during the natural aging process of healthy adults.Methods:A total of 647 Chinese healthy adults who underwent health check-ups at the Second Affiliated Hospital of Zhejiang University School of Medicine and Songyang County People's Hospital, from January 2017 to September 2024 were collected. There were 277 males and 370 females, aged 18-93 years. Anteroposterior and lateral X-ray films of the whole spine were taken to evaluate the spinal-pelvic sagittal morphology. The following parameters were measured: thoracic kyphosis (TK), lumbar lordosis(LL), sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT), global tilt (GT), T 1-pelvic angle (TPA), sagittal vertical axis (SVA), thoracic Cobb angle (T-Cobb), lower end vertebra of thoracic Cobb angle (T-LEV), apex vertebra of thoracic Cobb angle (T-Apex), lumbar Cobb angle (L-Cobb). Compare the differences in spine-pelvis parameters among patients of different genders and age groups (in this study, the subjects were subdivided into the 18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-93 years groups according to the age range). Results:The results showed that GT, SVA, TPA, and PT increased with age ( P<0.05). For males aged 18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-93 years, PT values were 8.58°±6.47°, 9.60°±5.63°, 12.65°±7.13°, 11.00°±6.99°, 13.01°±8.63°, 15.77°±8.02°, and 18.47°±10.03° respectively; for females in the same age groups, the PT values were 8.44°±6.83°, 9.00°±6.44°, 11.84°±7.35°, 12.07°±7.51°, 15.44°±9.39°, 19.26°±8.28°, and 18.17°±9.43° respectively. For males in these age groups, the global tilt (GT) values were 6.37°±7.20°, 8.77°±6.51°, 10.38°±9.07°, 8.80°±7.49°, 10.80°±8.62°, 16.07°±10.42°, and 21.99°±12.65° respectively; for females, the GT values were 4.46°±8.09°, 5.96°±7.83°, 8.17°±6.88°, 9.41°±8.03°, 9.96°±1.39°, 17.89°±9.39°, and 19.55°±12.34° respectively. The sagittal vertical axis (SVA) values for males in the age groups were -7.94±25.57 mm, -2.98±25.69 mm, -4.63±20.90 mm, -6.43±32.81 mm, 7.85±43.39 mm, 36.49±53.89 mm, and 55.57±51.10 mm respectively; for females, they were -24.12±31.35 mm, -17.49±25.12 mm, -17.88±22.72 mm, -8.25±30.91 mm, 8.80±27.45 mm, 28.67±38.22 mm, and 23.23±35.19 mm respectively. For males, the thoracic pelvic angle (TPA) values across the age groups were 4.46°±5.94°, 6.05°±5.38°, 9.58°±9.35°, 7.52°±7.64°, 11.23°±9.59°, 16.32°±12.38°, and 18.49°±11.70° respectively; for females, the TPA values were 2.72°±6.88°, 3.68°±6.26°, 7.30°±6.11°, 7.44°±6.75°, 12.64°±9.79°, 19.08°±10.39°, and 16.79°±13.19° respectively. T-Cobb, T-LEV, and T-Apex increased slowly with age ( P<0.05). The pelvic incidence (PI) remained relatively constant in males ( P>0.05), while it increased slowly with age in females ( P<0.05). Conclusions:Sagittal anteversion of the spinal-pelvis increases with age. Gender differences are reflected in specific changes in the fluctuation amplitude of certain parameters (such as PI), and the fluctuations of indicators like T-Cobb, T-LEV, and T-Apex are closely related to the natural aging process of the spine.