ObjectiveTo investigate the key targets of Jianpi Yiqi prescription （JYP） in the treatment of hepatocellular carcinoma （HCC） based on network pharmacology and explore the effect of JYP on the invasion and proliferation of hepatocellular carcinoma cells via protein tyrosine phosphatase， non-receptor type 1 （PTPN1） by bioinformatics analysis and CRISPR/Cas9. MethodsThe potential targets of JYP in the treatment of HCC were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， SwissTargetPrediction， GeneCards， NCBI， and CTD. Additionally， the active components of JYP that could interact with PTPN1 were screened out， and then molecular docking between the targets and active components was performed in Autodock 4.0. UALCAN， HPA， and LinkedOmics were used to analyze the expression of PTPN1 in the HCC tissue， and the relationship of PTPN1 expression with the overall survival （OS） of HCC patients was discussed. CRISPR/Cas9 was used to knock down the expression of PTPN1 in HepG2 and SK-hep-1 cells， and the knockdown effect was examined by sequencing， Real-time PCR， and Western blot. HepG2 cells were classified into blank control， low-， medium-， and high-dose JYP （5.25， 10.5， 21 g·kg^-1）， and PTPN1 knockout groups. Real-time PCR and Western blot were employed to determine the mRNA and protein levels， respectively， of PTPN1 in HepG2 cells of each group. The effects of JYP and PTPN1 knockdown on the proliferation， invasion， and apoptosis of HepG2 cells were detected by Cell Counting Kit-8 （CCK-8）， Transwell， and Annexin V-FITC/PI methods， respectively. ResultsJYP had the most active components targeting PTPN1， and 31 of the active components had the binding energy less than -5.0 kcal·mol^-1 in molecular docking. The mRNA and protein levels of PTPN1 in the HCC tissue were higher than those in the normal tissue （P<0.01）. Compared with that in the normal tissue， the mRNA level of PTPN1 in the HCC tissue was up-regulated at the pathological stages Ⅰ-Ⅲ and grades G₁-G₃ （P<0.01）， and it was not significantly up-regulated at the stage Ⅳ or grade G₄. The mRNA level of PTPN1 in the TP53-mutated HCC tissue was higher than that in the TP53-unmutated HCC tissue （P<0.01）. The high mRNA level of PTPN1 was associated with the OS reduction （P<0.01）. After treatment with the JYP-containing serum or knockdown of PTPN1， HepG2 cells demonstrated decreased proliferation and invasion and increased apoptosis （P<0.01）. ConclusionPTPN1 may be one of the core targets of JYP in the treatment of HCC. It is highly expressed in the HCC tissue and cells， which is associated with the poor prognosis of patients. The expression level of PTPN1 is significantly up-regulated in the HCC tissue of the patients with TP53 mutation. However， TP53 mutation or deletion does not affect the expression of PTPN1 in HCC cells. JYP can significantly down-regulate the expression of PTPN1 to inhibit the proliferation and invasion and promote the apoptosis of HCC cells.

Purpose: The optimal reconstruction method following distal gastrectomy has not been elucidated. Since Billroth-II (B-II) reconstruction is commonly associated with increased bile reflux, Braun jejunojejunostomy has been proposed to reduce this complication. Materials and Methods: We retrospectively analyzed 325 patients with gastric cancer who underwent distal gastrectomy with B-II reconstruction between January 2015 and December 2017, comprising 159 patients without Braun anastomosis and 166 with Braun anastomosis.Outcomes were assessed over three years using annual gastroscopy based on the residual food, gastritis, and bile reflux criteria and the Los Angeles classification for reflux esophagitis. Results: In the first postoperative year, the group with Braun anastomosis showed a significant reduction in bile reflux compared to the group without Braun anastomosis (75.9% vs. 86.2%; P=0.019). Moreover, multivariate analysis identified Braun anastomosis as the sole factor associated with this outcome. Additionally, the group with Braun anastomosis had a lower incidence of heartburn (12.0% vs. 20.1%; P=0.047) and reduced use of prokinetics (P<0.001) and acid reducers (P=0.002) compared to the group without Braun anastomosis.However, these benefits diminished in subsequent years, with no significant differences in residual food, gastritis, or reflux esophagitis between the groups. Both groups showed similar body mass index scores and nutritional outcomes over the 3-year follow-up period. Conclusions Although Braun anastomosis offers short-term benefits in reducing bile reflux after B-II reconstruction, these effects are not sustainable. The routine use of Braun anastomosis should be reconsidered, though either approach remains a viable option depending on the patient’s circumstances.

Purpose: The optimal reconstruction method following distal gastrectomy has not been elucidated. Since Billroth-II (B-II) reconstruction is commonly associated with increased bile reflux, Braun jejunojejunostomy has been proposed to reduce this complication. Materials and Methods: We retrospectively analyzed 325 patients with gastric cancer who underwent distal gastrectomy with B-II reconstruction between January 2015 and December 2017, comprising 159 patients without Braun anastomosis and 166 with Braun anastomosis.Outcomes were assessed over three years using annual gastroscopy based on the residual food, gastritis, and bile reflux criteria and the Los Angeles classification for reflux esophagitis. Results: In the first postoperative year, the group with Braun anastomosis showed a significant reduction in bile reflux compared to the group without Braun anastomosis (75.9% vs. 86.2%; P=0.019). Moreover, multivariate analysis identified Braun anastomosis as the sole factor associated with this outcome. Additionally, the group with Braun anastomosis had a lower incidence of heartburn (12.0% vs. 20.1%; P=0.047) and reduced use of prokinetics (P<0.001) and acid reducers (P=0.002) compared to the group without Braun anastomosis.However, these benefits diminished in subsequent years, with no significant differences in residual food, gastritis, or reflux esophagitis between the groups. Both groups showed similar body mass index scores and nutritional outcomes over the 3-year follow-up period. Conclusions Although Braun anastomosis offers short-term benefits in reducing bile reflux after B-II reconstruction, these effects are not sustainable. The routine use of Braun anastomosis should be reconsidered, though either approach remains a viable option depending on the patient’s circumstances.

This review described the potential health threats to the cardiovascular system from micro-nano plastics (MNPs) and their multifaceted toxicity mechanisms. The article reviewed the environmental distribution of MNPs, exposure pathways, and their toxic effects on the cardiovascular system, and summarized the specific mechanisms of MNPs involving oxidative stress, inflammatory response, mitochondrial damage, apoptosis, pyroptosis, and autophagy dysregulation. Meanwhile, the combined toxic effects of MNPs with other environmental pollutants (e.g., heavy metals and polycyclic aromatic hydrocarbons), including synergistic, antagonistic, and dual effects, were analyzed, and the potential risks of MNPs as carriers of microorganisms and toxic chemicals were pointed out. The widespread presence of MNPs and their complex toxicity mechanisms may make them important triggers for cardiovascular diseases, but current research still suffers from unbalanced studies across environmental systems, incomplete understanding of plastic properties, and limited knowledge of long-term biological effects. Future research should focus on the long-term effects of MNPs, the joint toxicity mechanisms with other pollutants, and the differential effects across population subgroups. It is suggested to accelerate plastic recycling technology innovation, promote biodegradable materials, and optimize waste treatment process to mitigate the potential threat of MNPs pollution to human health. Through multidisciplinary collaboration and in-depth research, combining innovative concepts from toxicology, public health policy, and environmental science, it is expected to provide new methods and approaches for the prevention and treatment of cardiovascular diseases associated with MNPs.

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

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*

A complete plant body consists of elements on different scales, including microscopic molecules, mesoscopic multicellular structures, and macroscopic tissues and organs, which are interconnected to form complex biological networks. The growth and development of plants involve the regulation of elements on different scales and their biological networks, which requires the coordinated operation of multiple molecules, cells, tissues, and organs. It is difficult to reveal the essence of multi-level life activities by a single method or technology. In recent years, the development of various novel imaging technologies has provided new approaches for revealing the complex life activities in plants. Using multi-modal imaging technologies to study the cross-scale network connections of plants from the microscopic, mesoscopic, and macroscopic levels is crucial for understanding the complex internal connections behind biological functions. This paper first summarizes multi-modal cross-scale imaging technologies, three-dimensional reconstruction, and image processing methods, outlines the basic framework of cross-scale network connection properties, and then summarizes the applications of multi-modal imaging technologies in elucidating plant multi-scale networks. Finally, this review systematically integrates the combined analysis of cross-scale 3D spatial structural data and single-cell omics, laying a theoretical foundation for the innovation of novel plant imaging technologies. Furthermore, it provides a new research paradigm for in-depth exploration of the interaction mechanisms among cross-scale elements and the principles of biological network connectivity in plant life activities.
Plants/metabolism* ; Imaging, Three-Dimensional/methods* ; Image Processing, Computer-Assisted/methods* ; Multimodal Imaging/methods* ; Plant Physiological Phenomena

Objective:To evaluate the clinical efficacy of Cai's gynecological nourishing kidney therapy for patients with diminished ovarian reserve (DOR).Methods:A randomly controlled trail was conducted. A total of 63 patients with DOR who were treated in the gynecology outpatient clinic of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine from September 2020 to January 2022 were set as observation subjects, and were divided into control group ( n=31) and observation group ( n=32) according to the random number table method. The patients in the control group were treated with Femoston, and the patients in the observation group were treated with Cai's gynecological nourishing kidney therapy on the basis of Femoston treatment. Both groups were treated for 3 menstrual cycles. Both antral follicle count (AFC) was performed by vaginal ultrasound, serum levels of TGF-β1, IL-1β, IL-2, IL-6 and IL-21 were detected by ELISA, and serum levels of FSH, LH, E2, anti-Müllerian hormone (AMH) and MDA were detected by biochemical methods. The TCM syndrome score was used to evaluate the severity of symptoms, and the menstrual score was used to evaluate the abnormal menstruation. Clinical efficacy was evaluated. Results:The total effective rate was 87.50% (28/32) in the observation group and 58.06% (18/31) in the control group, with statistical significance ( χ2=8.42, P=0.004). After treatment, the AFC in the observation group (3.93±2.32 vs. 2.21±2.18, t=3.03) was higher than that of the control group ( P<0.01). After treatment, the serum FSH level of the observation group [10.05 (8.35, 21.48) IU/L vs. 20.60 (8.00, 43.30) IU/L, Z=2.18] was lower than that of the control group ( P<0.05), and the level of AMH [0.19 (0.03, 0.47) μg/L vs. 0.02 (0.01, 0.24) μg/L, Z=-1.54] in the observation group was higher than that of the control group ( P<0.05). The serum levels of TGF-β1 [(68.27±11.76) ng/L vs. (55.33±13.03) ng/L, t=4.14] and IL-1β [(58.00±7.53) ng/L vs. (52.31±8.06) ng/L, t=2.89] in the observation group were higher than those in the control group, and the levels of IL-6 [(33.26±7.45) ng/L vs. (40.69±11.69) ng/L, t=3.02], the level of IL-21 [(118.37±15.56) ng/L vs. (140.43±25.51) ng/L, t=-4.04] was lower than that of the control group ( P<0.01). Conclusions:Cai's gynecological nourishing kidney therapy combined with Fenmaotong can effectively increase the AFC of DOR patients and improve clinical efficacy. Its mechanism of action may be related to reducing serum FSH and LH levels and increasing E2 levels.

Objective To analyze the incidence,colonization pathways,and predictive factors of bacterial colonization of epidural analgesia catheters in patients with chronic pain.Methods A total of 150 patients with chronic pain who underwent continuous epidural catheterization(catheter in-dwelling time of 7 to 10 days)were selected as study subjects.Samples from three sites were collect-ed for bacterial culture.Clinical data of the patients were collected,and the positive rate of bacterial culture,characteristics of bacterial species distribution,and bacterial colonization pathways were ana-lyzed.The efficacy of predictive factors was assessed using the receiver operating characteristic(ROC)curve.Results The positive rates of bacterial culture in samples from the skin swabbing fluid around the puncture site,the subcutaneous segment of the catheter,and the catheter tip were 22.0％,7.3％,and 8.7％,respectively.Staphylococcus epidermidis was the predominant colonizing bacterial species.Spearman correlation coefficient analysis showed a significant correlation between the results of bacterial culture from the skin around the puncture site and catheter tip colonization(r=0.47,P＜0.01).ROC curve analysis revealed that the area under the curve of bacterial culture results from the skin around the puncture site in predicting catheter tip bacterial colonization was 0.843,with a sensitivity of 84.9％and a specificity of 84.6％.Conclusion Bacterial migra-tion along the catheter is the main pathway for catheter tip bacterial colonization,and the results of bacterial culture from the skin around the puncture site are an effective predictive factor for the risk of bacterial colonization.