Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

ObjectiveTo address the key challenges in breast electrical impedance tomography (EIT) reconstruction including the severe ill‑posedness of the inverse problem, limited measurement information from the electrodes, low contrast of small lesions, as well as the common drawbacks of traditional reconstruction methods such as boundary blurring, low spatial resolution, and weak small-target detection capability, and to overcome the limitations of existing deep learning approaches namely low training efficiency, insufficient physical consistency, and substantial information loss during the low‑to‑high dimensional mapping process, this study proposes a multi‑scale attention and dynamic sparse mask fusion network (MADS‑Net). The proposed method aims to enhance high‑resolution reconstruction accuracy, small-lesion detectability, noise robustness, and computational efficiency in breast‑screening-oriented EIT, thereby providing a feasible solution for the application of EIT in breast functional imaging. MethodsThe proposed network adopts a strategy of “locate first, reconstruct later”. It realizes adaptive allocation of computational resources through a dynamic mask module, alleviates information loss in the low-to-high dimensional mapping process via a multi-scale attention mechanism, and embeds physical constraints to improve the physical rationality of reconstruction results. The performance of the proposed method was validated through systematic numerical simulations, agar phantom experiments, and porcine tissue experiments. Comparisons were made with mainstream methods including the Gauss-Newton algorithm, convolutional neural networks, U-Net, and Deep D-Bar. The image correlation coefficient (ICC), root mean square error (RMSE), and peak signal-to-noise ratio (PSNR) were adopted as quantitative evaluation metrics. Furthermore, lesion‑level evaluation metrics were introduced to assess the capability of different methods in reconstructing abnormal target boundaries and small‑sized target regions. ResultsExperimental results demonstrate that MADS-Net outperforms all comparison methods across all test scenarios. In numerical simulations, it achieves higher accuracy in target morphology and spatial location recovery as well as better background suppression. In agar phantom experiments, its detection and imaging reliability for small targets is significantly superior to the comparison methods. In porcine tissue experiments, the model maintains good generalization performance and can adapt to complex biological tissue imaging scenarios. Quantitative results show that MADS-Net achieves an average ICC of 0.917 6±0.048 8, an RMSE as low as0.060 6±0.031 6, and a PSNR of (23.893 9±2.685 3) dB. It successfully detects tiny targets as small as 5 mm within a 100 mm diameter sensing field, reduces the total training duration by 23.5% compared with the baseline method, and maintains stable reconstruction performance even under strong noise interference. ConclusionThe results demonstrate that MADS-Net achieves favorable EIT reconstruction performance in numerical simulations, agar phantom experiments, and porcine tissue experiments, even under common practical imaging challenges including low signal-to-noise ratio and blurred tissue boundaries. This study provides a methodological reference for further research on EIT in breast-screening-related scenarios and other medical functional imaging tasks, and also offers a low-cost, radiation-free alternative for breast lesion screening that aligns with the clinical demand for non-invasive diagnostic tools. It should be noted that real clinical breast data have not yet been used for validation in this study, and the clinical applicability of the proposed method requires further investigation. Future work will prioritize collecting multi-center real clinical breast datasets, and further optimize the model’s generalization ability to adapt to individual differences in breast tissue composition to promote its clinical application.

ObjectiveTo develop a carbon nanoparticle-manganese dioxide (CN-MnO₂) injection integrating visually identifiable staining and magnetic resonance (MR) T₁/T₂ dual-modal imaging, and to systematically evaluate its physicochemical properties, critical quality attributes, biocompatibility, and efficacy for gastrointestinal marking and localization. MethodsCN-MnO₂ was prepared using a mild liquid-phase in situ redox deposition strategy and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The pH of CN-MnO₂ was directly measured using a pH meter. The osmolality pressure of CN-MnO₂ was determined by the freezing point depression method. The bacterial endotoxin was detected using the gel-clot Limulus amebocyte lysate test, which did not rely on absorbance readings. The appearance of the CN-MnO₂ injection solution stored at 4 ℃ under light shielding and sealed for 0, 5, and 10 days was observed, and its hydrated particle size, polydispersity index, zeta potential, and pH were also measured. With gadopentetate dimeglumine (Gd-DTPA) as the positive control, different concentration gradients were established, and T₁ and T₂ relaxation times were measured to construct concentration-dependent plots of the longitudinal and transverse relaxation rates (R₁ and R₂) and calculate the corresponding relaxivities (r₁ and r₂), compare relaxivity performance, and determine the working concentration for subsequent in vivo experiments. Cytocompatibility was assessed using the methyl thiazolyl tetrazolium (MTT) assay and live/dead staining. Sixteen male 6-week-old SD rats were randomly assigned to an experimental group and a control group (n=8 per group) and subcutaneously injected with CN-MnO₂ injection at a total Mn concentration of 0.80 mmol/L or an equal volume of normal saline, respectively. Short-term in vivo safety was evaluated by regular body weight monitoring, hematoxylin-eosin (HE) staining of major organs, hematological and serum biochemical analyses, inflammatory cytokine detection, and inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. Eight male 5–6-month-old Bama minipigs were randomly assigned to a CN-MnO₂ group (n=6) and a carbon nanoparticle suspension injection (CNSI) group (n=2). CN-MnO₂ injection or CNSI was injected subserosally into the stomach, small intestine, and colon. Within 5 min after each injection, the maximum staining diameter at each injection site was measured and recorded. MR T1WI/T2WI scans were performed on days 3 and 7 after injection to evaluate MR visualization at the injection sites. At the end of observation, the injection sites and major organs were collected for histopathological evaluation by hematoxylin-eosin staining. ResultsCN-MnO₂ appeared as a black suspension, with no obvious aggregation or sedimentation after standing at room temperature (20-25 ℃) for 15 days. Its average hydrodynamic diameter was approximately (228.7±15.3) nm, the polydispersity index was 0.184±0.021, and the zeta potential was (-24.6±2.8) mV. XPS showed that CN-MnO₂ was mainly composed of C, O, and Mn, with oxygen accounting for approximately 68.82%. The Mn 2p spectrum exhibited two characteristic peaks at 642.4 and 653.1 eV. XRD indicated that low-crystallinity δ-MnO₂ was dispersed within the carbon matrix. The pH was 6.82±0.06, the osmolality was (298.4±6.7) mOsm/kg, and the bacterial endotoxin level was below the detection limit. In vitro MR imaging showed a clear concentration-dependent response, with r₁ and r₂ values of 9.6 L·mmol^-1·s^-1 and 17.2 L·mmol^-1·s^-1, respectively, indicating favorable T₁/T₂ contrast performance superior to that of Gd-DTPA. At 0.80 mmol/L, CN-MnO₂ showed no obvious cytotoxicity in vitro. Short-term safety evaluation in SD rats revealed no obvious inflammatory response, impairment of liver or renal function, or abnormal manganese accumulation in major organs. In Bama minipigs, the mean staining diameters of the CN-MnO₂ group in the stomach, small intestine, and colon were (0.65±0.12) cm, (0.61±0.11) cm, and (0.58±0.10) cm, respectively, with no significant difference among the three injection sites (P>0.05). The overall mean staining diameter was smaller in the CN-MnO₂ group than in the CNSI group (P<0.05). MR examinations showed that the injection sites were identifiable on both day 3 and day 7, with stronger signals observed on day 3. At the end of observation, no obvious pathological abnormalities were observed at the injection sites or in major organs. ConclusionA CN-MnO₂ injection with uniform particle size and stable physicochemical properties can be successfully prepared. This formulation integrates visible gastrointestinal staining with MR T₁/T₂ dual-modal imaging, providing a new strategy for preoperative gastrointestinal marking and localization as well as precise intraoperative resection.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective To retrieve,evaluate and summarize the best evidence for blood glucose monitoring and management in patients with diabetes of the exocrine pancreas(DEP),and to provide evidence-based basis for clinical practice.Methods According to the"6S"evidence model,relevant evidence on blood glucose management in patients with DEP was searched from computer decision support systems,guideline networks,professional association websites and databases from top to bottom,covering clinical decision-making,clinical practice guidelines,evidence summaries,systematic reviews,expert consensuses,and randomized controlled trials.The search scope was from the establishment of the databases to June 30,2024.Totally 2 researchers independently evaluated the quality of the included literature,and extracted data and summarized evidence that met the criteria.Results A total of 10 articles were included,including 3 guidelines,1 expert consensus,2 systematic reviews,l clinical decision,1 RCT,and 2 cohort studies.Finally,26 pieces of best evidence were formed from 5 aspects,including blood glucose management team construction and goals,blood glucose monitoring methods,glucose control medication management,lifestyle health education and treatment of hypoglycemia.Conclusion This study summarizes the best evidence for blood glucose monitoring and management in DEP patients,which can provide resource preparation for clinical translation and a basis for medical staff to carry out blood glucose management in DEP patients.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective To retrieve,evaluate and summarize the best evidence for blood glucose monitoring and management in patients with diabetes of the exocrine pancreas(DEP),and to provide evidence-based basis for clinical practice.Methods According to the"6S"evidence model,relevant evidence on blood glucose management in patients with DEP was searched from computer decision support systems,guideline networks,professional association websites and databases from top to bottom,covering clinical decision-making,clinical practice guidelines,evidence summaries,systematic reviews,expert consensuses,and randomized controlled trials.The search scope was from the establishment of the databases to June 30,2024.Totally 2 researchers independently evaluated the quality of the included literature,and extracted data and summarized evidence that met the criteria.Results A total of 10 articles were included,including 3 guidelines,1 expert consensus,2 systematic reviews,l clinical decision,1 RCT,and 2 cohort studies.Finally,26 pieces of best evidence were formed from 5 aspects,including blood glucose management team construction and goals,blood glucose monitoring methods,glucose control medication management,lifestyle health education and treatment of hypoglycemia.Conclusion This study summarizes the best evidence for blood glucose monitoring and management in DEP patients,which can provide resource preparation for clinical translation and a basis for medical staff to carry out blood glucose management in DEP patients.

Objective To analyze the medication rules of national patented Chinese herbal compounds for the treatment of diabetic peripheral neuropathy(DPN)by data mining method,and to provide reference for clinical medication.Methods The patents of Chinese medicine compound for the treatment of DPN were retrieved from the website of the China National Intellectual Property Administration(CNIPA).Excel 2021 was used for frequency statistics.RAW Graphs 2.0 was used to make a Sankey diagram of the efficacy of high-frequency Chinese medicinals.SPSS Statistics 25.0 software was used for hierarchical cluster analysis of the medicines,and the core prescriptions were mined based on Cytoscape 3.9.1.Results A total of 101 patented prescription were included,involving 243 herbs.The top three Chinese medicines in the descending order of occurrence frequency were Salviae Miltiorrhizae Radix et Rhizoma,Astragali Radix,and Paeoniae Radix Alba.Most of the medicines of patented Chinese medicine compounds for the treatment of DPN were warm and mild in nature,sweet,bitter and pungent in flavor,and had the meridian tropism of liver,heart and spleen meridians.According to the therapeutic actions,the medicine can be divided into tonic drugs,blood-activating and stasis-removing drugs,exterior-releasing drugs,liver-calming and wind-extinguishing drugs,heat-clearing drugs,bleeding-arresting drugs,mind-calming drugs,and urination-promoting and dampness-percolating drugs.The association rule analysis revealed the drug combination of Astragali Radix and Angelicae Sinensis Radix with the highest support.After hierarchical cluster analysis,the top 31 Chinese medicinals were classified into 7 groups.The core prescription which was composed of 7 medicines,namely Astragali Radix,Chuanxiong Rhizoma,Spatholobi Caulis,Salviae Miltiorrhizae Radix et Rhizoma,Achyranthis Bidentatae Radix,Cinnamomi Ramulus and Angelicae Sinensis Radix was finally mined out.Conclusion The treatment of DPN with patented Chinese herbal compounds is based on the therapies of supplementing deficiency,activating blood and removing stasis,and warming and unblocking meridians and collaterals.Meanwhile,consolidating the acquired foundation by strengthening spleen and soothing liver is also stressed.Clinically,the herbal pairs of Astragali Radix-Angelicae Sinensis Radix,Paeoniae Radix Alba-Salviae Miltiorrhizae Radix et Rhizoma are the optional drugs,and the core prescription composed of Astragali Radix,Chuanxiong Rhizoma,Spatholobi Caulis,Salviae Miltiorrhizae Radix et Rhizoma,Achyranthis Bidentatae Radix,Cinnamomi Ramulus and Angelicae Sinensis Radix can be used for the whole course of DPN.

Objective:To investigate the efficacy and safety of injectable modified sodium hyaluronate gel DX23 in filling and treating midface depression.Methods:A prospective, randomized, multicenter, "no treatment" controlled study was conducted. Patients with midface depression who were treated from March 2019 to February 2021 at Beijing Anzhen Hospital Affiliated to Capital Medical University, Qilu Hospital of Shandong University, and Jining First People’s Hospital were enrolled. Patients were randomized using a stratified block randomization method with a random function list. The experimental group received injectable modified sodium hyaluronate gel DX23 to treat midface depression. The concentration of sodium hyaluronate in DX23 was 23 mg/ml. The syringe was inserted perpendicularly to the skin at a 90-degree angle, and the injection layers were the superficial periosteum or the subcutaneous layer. The injection volume ranged from 1 to 6 ml. The control group received no treatment. The upper boundary of the midface extended outward from the zygomatic arch to the upper margin of the helix and inward to the line connecting the outer canthus. The lower boundary was the line connecting the corner of the mouth to the earlobe. Researchers used the midface aesthetic scales (MAS) response rate at 6 months post-injection as the primary indicator to evaluate the efficacy in improving the severity of midface depression. A reduction of 1 point in the MAS score compared to pre-treatment was considered a response, i. e., effective. Secondary indicators included the MAS response rates at 6 and 12 months after the last treatment (MAS response rate=number of MAS responders/total cases × 100%), the average change in three-dimensional midface volume images, the global aesthetic improvement scale (GAIS) response rate, patient satisfaction regarding the degree of improvement in midface volume, and monitoring of adverse reactions. Data analysis was performed using SPSS 25.0, SAS 9.04, and StataIC 15.0 software. The full analysis set (FAS) and the per-protocol set (PPS) were selected for analysis. Inferential analysis used t-tests and chi-square tests, with P<0.05 considered statistically significant. Results:A total of 164 patients were enrolled. The experimental group included 134 patients (7 males and 127 females) with an average age of 43.0±9.7 years (ranging from 21.6 to 66.6 years). The control group included 30 patients (5 males and 25 females) with an average age of 39.3±11.1 years (ranging from 25.6 to 43.5 years). The experimental group received bilateral midface depression filling, with an initial use of injectable modified sodium hyaluronate gel DX23 at a volume of (4.07±1.28) ml. In the experimental group, 3 cases were lost to follow-up at 30 days, 2 cases at 60 days, and 10 cases were excluded due to protocol violations. Fifteen patients entered FAS but not PPS. Ultimately, 119 patients completed the trial. The MAS response rates in the experimental group at 6 and 12 months post-treatment were 94.96% (113/119) and 56.30% (67/119), respectively. The control group’s MAS response rate at 6 months was 3.33% (1/30). At the 6-month follow-up post-treatment, the GAIS response rates evaluated by researchers and patients in the experimental group were 97.48% (116/119) (PPS) and 97.69% (27/30) (FAS), respectively. In the control group, the GAIS response rate evaluated by researchers was 3.33% (1/30) (FAS, PPS), and the patient GAIS response rate was 0% (0/30) (FAS, PPS). There were statistically significant differences between the two groups in both researcher and patient GAIS response rates (both P<0.01). At 6 months post-injection, comparisons of midface volume changes from baseline between the experimental and control groups showed statistically significant differences [(1.65±1.40) ml (PPS) vs. (0.12±0.85) ml; (1.55±1.44) ml (FAS) vs. (0.12±0.85) ml; both P<0.001]. At the 6-month follow-up in the experimental group, 1 case was lost to follow-up. In the PPS, 81 patients were "satisfied, " 34 were "very satisfied, " and 3 were "neutral." In the control group, 29 patients were "neutral, " and 1 was "dissatisfied." A total of 128 patients in the experimental group experienced injection site reactions, including swelling, hardness, tenderness, pain, lumps (protrusions), and bruising. Over 75% of patients resolved spontaneously within 8 days. Three cases received hot compress treatment and resolved within 28 days. One case experienced swelling of the left lower eyelid 1 day after injection, which resolved after local compression for 3 months. In the control group, 1 case developed circulatory ischemia and carotid atherosclerosis 12 months after the trial began. Conclusion:Injectable modified sodium hyaluronate gel DX23 corrects midface depression through local volume augmentation and is characterized by safety and durability.