ObjectiveThis study aimed to investigate whether Bushen Tongluo prescription inhibits macrophage polarization by regulating the Wnt3a/β-catenin signaling pathway， thereby reducing epithelial-mesenchymal transition and excessive extracellular matrix deposition， in order to elucidate the anti-pulmonary fibrosis mechanisms of Bushen Tongluo prescription and provide a new theoretical basis for the clinical treatment of pulmonary fibrosis. MethodsFifty male Sprague-Dawley （SD） rats were randomly divided into a blank group， model group， pirfenidone group， and high- and low-dose Bushen Tongluo prescription groups. Except for the blank group， the pulmonary fibrosis model was established by intratracheal instillation of bleomycin. Intervention was initiated on day 28 after modeling. The high- and low-dose Bushen Tongluo prescription groups were administered Bushen Tongluo prescription at doses of 30.88， 15.44 g·kg^-1， respectively， by intragastric gavage. The pirfenidone group was administered pirfenidone capsules at 110 mg·kg^-1 by intragastric gavage. The blank and model groups were given an equal volume of normal saline by gavage， once daily for 90 days. After treatment， the level of transforming growth factor-β₁ （TGF-β₁） in bronchoalveolar lavage fluid （BALF） was detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in lung tissue and the collagen volume fraction were compared. The protein distribution and expression of E-cadherin， cytokeratin 19， α-smooth muscle actin （α-SMA）， vimentin， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ） in lung tissue were detected by immunohistochemistry. The protein distribution and expression of CD68， arginase-1 （Arg-1）， inducible nitric oxide synthase （iNOS）， Wnt3a， and β-catenin in lung tissue were detected by immunofluorescence. The protein expression of Wnt3a and β-catenin in lung tissue was detected by Western blot， and the mRNA expression of Wnt3a and β-catenin was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， a large number of inflammatory cells infiltrated the airway walls， alveolar spaces， and interstitial tissue in the model group， with obvious fibrous tissue hyperplasia. The level of TGF-β₁ in BALF was significantly increased. The protein expression of E-cadherin and cytokeratin 19 in lung tissue was decreased， whereas the protein expression of α-SMA， Vimentin， Wnt3a， β-catenin， Col Ⅰ， and Col Ⅲ was increased. The fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue were increased. The protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue were significantly increased （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement in inflammatory cell infiltration and fibrous tissue hyperplasia in the airway walls， alveolar spaces， and interstitial tissue， decreased TGF-β₁ levels in BALF， increased protein expression of E-cadherin and cytokeratin 19 in lung tissue， decreased protein expression of α-SMA， Vimentin， Col Ⅰ， and Col Ⅲ， decreased fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue， and decreased protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue （P<0.05， P<0.01）. ConclusionBushen Tongluo prescription can improve bleomycin-induced pulmonary fibrosis in rats by inhibiting epithelial-mesenchymal transition and reducing excessive extracellular matrix deposition. The mechanism may be related to inhibition of the Wnt3a/β-catenin signaling pathway and the macrophage polarization mediated by this pathway.

ObjectiveTo explore the effect of cluster scalp acupuncture combined with Taijiquan training on depressive symptom, motor function, activities of daily living, serum markers, as well as brain functional connectivity (FC) and network topological properties in patients with post-stroke depression (PSD). MethodsA total of 40 PSD patients in the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine from September, 2022 to September, 2023 were enrolled and randomly divided into control group (n = 20) and experimental group (n = 20). The control group received cluster scalp acupuncture alone, while the experimental group underwent Taijiquan training in addition, for four weeks. They were assessed with Hamilton Depression Scale-17 (HAMD-17), Fugl-Meyer Assessment (FMA) and Barthel Index (BI) before and after treatment, while the serum levels of dopamine (DA), 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected with enzyme-linked immunosorbent assay. Resting-state functional magnetic resonance imaging (rs-fMRI) was applied to assess brain FC, as well as the global efficiency (Eg) and small-world property (σ) of brain networks. ResultsThe scores of HAMD-17, FMA and BI improved in both groups (t > 2.922, P < 0.01) after treatment, and improved more in the experimental group than in the control group (t > 2.517, P < 0.05). The serum levels of DA and 5-HT increased in both groups (t > 2.637, P < 0.05), and increased more in the experimental group (t > 2.192, P < 0.05). The serum levels of IL-6 and TNF-α decreased in the experimental group after treatment (t > 4.059, P < 0.001), and they were less than those in the control group (t > 2.154, P < 0.05). FC between left middle frontal gyrus and right anterior cingulate gyrus, as well as between left hippocampus and right precuneus were higher in the experimental group than in the control group after treatment (t > 3.867, P < 0.001), while Eg and σ increased in both groups (t > 2.828, P < 0.05), and they were higher in the experimental group (t > 2.675, P < 0.05). ConclusionCombination of Taijiquan training is more effective on depressive symptoms, motor function and activities of daily living in PSD patients, which may be related to up-regulation of serum DA and 5-HT, reduction of inflammatory factors, enhancement of prefrontal-limbic system functional connectivity and optimization of brain network topological properties.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening complication associated with significant morbidity and healthcare burden. Despite advances in diabetes care, recurrent DKA remains common, often reflecting gaps in treatment adherence and patient education. Identifying predictors of recurrence is crucial for risk stratification and targeted intervention. Methodology: We conducted a retrospective observational study of all adult DKA admissions to a tertiary centre between 2001 and 2025. Electronic medical records were reviewed for demographic data, biochemical parameters, precipitating factors, and clinical outcomes. DKA was defined using standard biochemical criteria. Recurrent DKA was defined as ≥2 admissions during the study period. Factors associated with recurrent DKA admissions were analyzed. Patients under the age of 18 years and those with missing vital information were excluded. Results: A total of 667 DKA admissions, comprising 566 patients, were identified, of which 101 admissions (15.1%) were recurrent, involving 65 patients. Among recurrent DKA episodes, the most common precipitating factors were infection (64.4%) and insulin omission (62.4%). After multivariate analyses, patients with type 1 diabetes mellitus (T1DM) were more likely to develop recurrent DKA compared to those with type 2 diabetes mellitus (aOR 4.16; 95% confidence interval [CI] 2.58–6.70; p <0.001). Insulin omission was strongly associated with recurrent DKA (aOR 2.29; 95% CI 1.46–3.60; p <0.001). In contrast, baseline glycated hemoglobin and chronic kidney disease were not significantly associated with recurrence. Diabetic counseling during the first DKA admission did not reduce recurrent DKA. There were no significant differences in mortality (3.9% vs 6.2%, p = 0.524) or critical care admission rates (40.6% vs 38.7%, p = 0.718) between recurrent and first DKA episodes. Conclusion Recurrent DKA accounts for a substantial proportion of DKA admissions and is strongly associated with insulin omission and T1DM. Our findings suggest that recurrent DKA is driven predominantly by behavioral and adherencerelated factors, indicating the need for multidisciplinary interventions beyond standard inpatient counseling.
Diabetic Ketoacidosis ; Retrospective Studies

Introduction: Diabetic ketoacidosis (DKA) in pregnancy is an uncommon yet life-threatening emergency, with disproportionate risks to both mother and fetus. Pregnancy-specific physiological changes predispose patients to rapid metabolic decompensation, often with atypical presentations. Despite this, local data remain limited. We describe the clinical profile, precipitating factors, and outcomes of DKA in pregnancy in a tertiary centre, with emphasis on potentially preventable triggers. Cases: Nine pregnant patients with DKA were identified from a retrospective review of all cases admitted for DKA from 2002 to 2025. Mean age was 31.67 ± 5.20 years; all were Malay. The majority had type 2 diabetes mellitus (55.6%), followed by type 1 diabetes (33.3%) and latent autoimmune diabetes in adults (11.1%). The mean period of amenorrhea was 19.67 ± 12.62 weeks. Infection was the leading precipitant (44.4%), with additional triggers including insulin omission (22.2%), hyperemesis gravidarum, preterm labor, steroid exposure, and perioperative fasting. Most diagnoses were made in the emergency department (55.6%). Biochemical parameters reflected significant severity (mean bicarbonate 7.89 ± 2.98 mmol/L; anion gap 25.00 ± 5.81), with 88.9% classified as severe DKA. Intensive Care Unit (ICU) care was required in 77.8% of cases. The majority (77.8%) were admitted to the ICU unit, with a median time to resolution of 13.00 ± 12.00 hours (interquartile range [IQR]), and the median hospital length of stay was 7.00 ± 5.00 days (IQR). Complications during treatment included hypokalemia (33.3%), acute kidney injury (22.2%), and hypoglycemia (11.1%). Rebound DKA occurred in one-third of patients. All patients were discharged clinically stable. Outcome data demonstrated pregnancy loss in three cases and one preterm birth. Conclusion DKA in pregnancy remains a severe and resource-intensive condition. This series highlights missed opportunities in prevention, with modifiable precipitants such as infection and insulin omission commonly identified. The high severity at presentation suggests delays in recognition. Early detection, optimized metabolic care, and targeted preventive strategies are crucial to improving maternal and fetal outcomes.
Female ; Pregnancy ; Diabetic Ketoacidosis

ObjectiveTo explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments. MethodsThe drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules， and constipation-related targets were collected from disease databases. A protein-protein interaction （PPI） network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets， which was followed by gene ontology （GO） function and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analyses. A "bioactive component-target-pathway" network was constructed， and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network. Molecular docking was employed to predict the binding affinity of core components to key targets. A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation. ResultsThe PPI network revealed six key constipation-related targets： protein kinase B （Akt1）， B-cell lymphoma-2 （Bcl-2）， glycogen synthase kinase-3β （GSK-3β）， cyclooxygenase-2 （PTGS2）， estrogen receptor 1 （ESR1）， and epidermal growth factor receptor （EGFR）. The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway was the most enriched. The topological parameter analysis of the "bioactive component-target-pathway" network screened out the top 10 core components： auranetin， isosinensetin， naringin， diosmetin， quercetin， apigenin， luteolin， hesperidin， isorhapontigenin， and chrysophanol. Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets. Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules， the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propulsion rate of mice were improved. After treatment with Shouhui Tongbian capsules， the colonic mucosal injury and glandular arrangement were alleviated， and the muscle layer thickness was increased. Western blot results showed that Shouhui Tongbian capsules recovered the expression of apoptosis-related molecules mediated by the PI3K/Akt pathway in the colonic tissue of constipated mice. Terminal-deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） results showed that the cell apoptosis rate of the colon significantly reduced after intervention with Shouhui Tongbian capsules. ConclusionThe results of network pharmacology and animal experiments confirmed that Shouhui Tongbian capsules can treat constipation through multiple targets and pathways. The capsules can effectively intervene in loperamide-induced constipation in mice by regulating the constipation indicators and reducing cell apoptosis in the colon tissue via activating the PI3K/Akt signaling pathway.

Robot-assist partial nephrectomy is widely used in the operative treatment of localized renal cell carcinoma.In recent years, with the rapid development of the surgical robot and 5G communication technology, robtic remote partial nephrectomy has also been rapidly applied, which has a few of advantages such as low trauma, high accuracy, the breakthrough in space restriction and wide application, but it also faces many challenges such as privacy protection, economic cost, network stability and ethical issues.It may be more widely used in many special scenarios such as battlefield rescue in the future. The current situation and future of robotic partial nephrectomy are discussed in this article.

Objective To explore the effect of nuclear respiratory factor 1(NRF1)activation of ATP binding cas-sette transporter C1(ABCC1)transcription on cisplatin resistance in lung adenocarcinoma cells and its potential mechanisms.Methods The expression levels of ABCC1 in lung adenocarcinoma tumor tissues were analyzed by on-cogenomic datasets.Cells were grouped into:sh-NC,sh-ABCC1,sh-NC+oe-NC,sh-NRF1+oe-NC and sh-NRF1+oe-ABCC1.Real-time polymerase chain reaction(RT-qPCR)was used to detect the expression of ABCC1 in lung adenocarcinoma cells.Cisplatin-resistant lung adenocarcinoma cell strains were constructed to detect the expression level of ABCC1.Cell proliferation,migration and invasion were assessed by colony formation and Transwell assay.The IC50 values of drug-resistant lung adenocarcinoma cells treated with different doses(0,0.001,0.002,0.004,0.008,0.016 and 0.032 mg/mL)of cisplatin were detected by CCK-8 assay.Western blot was used to detect the protein expression of epithelial-mesenchymal transition markers(E-cadherin,N-cadherin).Dual luciferase and ChIP assays were performed to verify the binding relationship between NRF1 and ABCC1.Results ABCC1 was highly expressed in lung adenocarcinoma tumor tissues and cells.Compared with cisplatin-sensitive lung adenocarci-noma cells,ABCC1 was highly expressed in cisplatin-resistant lung adenocarcinoma cells,and knockdown of ABCC1 significantly inhibited cell proliferation,migration and invasion,and increased the expression of E-cadherin(P<0.05)and decreased the expression of N-cadherin(P<0.05).Knockdown of ABCC1 significantly increased the sensitivity of lung adenocarcinoma cells to cisplatin(P<0.05).In addition,dual luciferase and ChIP experi-ments confirmed the binding relationship between NRF1 and ABCC1 promoter de-binding,and NRF1 could activate the transcription of ABCC1.Knockdown of NRF1 attenuated the inhibitory effect of over-expressed ABCC1 on the proliferation,migration,invasion and cisplatin-resistance of lung adenocarcinoma cells(P<0.05).Conclusions This study revealed the effect of the NRF1/ABCC1 axis enhancement is a potential strategy to overcome the barrier of cisplatin-resistance in chemotherapy of lung adenocarcinoma.

Objective To investigate the postoperative efficacy of laparoscopic hiatal hernia repair(LHHR)combined with Toupet or Dor fundoplication for the treatment of esophageal hiatal hernia(HH).Methods A retrospective analysis was conducted on the case data of HH patients who underwent LHHR combined with Toupet(Toupet group,n=53)and Dor(Dor group,n=53)fundoplication between December 2018 and December 2022 in Department of General Surgery of Gansu Provincial Hospital.Intraoperative and postoperative recovery outcomes of both groups were observed.We analyzed and compared the incidence of dysphagia and gastroesophageal reflux disease questionnaire(GERD-Q)scores at preoperative and postoperative intervals of 1 month,6 months,and 1 year.The incidence of postoperative complications and the 1-year recurrence rate were compared between the two groups.Additionally,factors influencing postoperative dysphagia within the first month were examined.Results The differences between the two groups in operation time,intraoperative bleeding,postoperative ventilation time,postoperative extubation time and hospitalization time were not statistically significant(P>0.05).There was no significant difference in the incidence of immediate postoperative dysphagia in two groups(P>0.05).Furthermore,the differences between the two groups in the incidence of postoperative complications,such as bloating,abdominal pain and diarrhea,were not statistically significant(P>0.05).The incidence of dysphagia in Toupet group was higher than that in Dor group at 1 month postoperatively,and the difference was statistically significant(P=0.017);but the difference in the incidence of dysphagia between the two groups at 6 months and 1 year postoperatively was not statistically significant(P=0.767,1.000).The results of binary logistic regression analysis showed that both surgical procedure(OR=2.613,95%CI 1.141-5.983,P=0.023)and esophageal contractile reserve function(OR=2.921,95%CI 1.203-7.095,P=0.018)were independent risk factors for the incidence of dysphagia in patients with HH at 1 month after surgery.Compared with the preoperative period,the GERD-Q symptom scores were lower in both groups at 1 month,6 months,and 1 year postoperatively,and the difference was statistically significant(P<0.05);but there was no statistically significant difference between the groups at the same time point(Fintergroup=0.334,P=0.565).The difference between the two groups in 1-year postoperative recurrence rates was not statistically significant(P>0.05).Conclusions LHHR combined with Toupet or Dor fundoplication are both safe and effective surgical procedures for the treatment of HH,with excellent reflux control,fewer complications and lower recurrence rates,but Toupet fundoplication is more likely to have postoperative short-term dysphagia than Dor fundoplication.

Clinically,intrahepatic cholangiocarcinoma(iCCA)is characterized by insidious onset and strong invasiveness.The vast majority of iCCA patients have already been in the middle and advanced stage of disease when the diagnosis is confirmed,and the prognosis is poorer.The therapeutic methods for the middle and advanced iCCA mainly consist of systemic therapy and local therapy.However,the efficacy of single-agent therapies is limited.Recent studies have demonstrated that comprehensive treatment strategies based on interventional approaches,such as ablation,transarterial chemoembolization(TACE),transcatheter radioembolization(TARE),hepatic arterial infusion chemotherapy(HAIC),and iodine-125(125I)seeds implantation can significantly improve survival rate for patients with middle and advanced iCCA,meanwhile effectively reducing the incidence of adverse events.This article aims to review the latest progress in the interventional treatment for iCCA.