Objective To explore the action mechanism of dehydrocostus lactone(DHL)on renal interstitial fibrosis(RIF)in rats with unilateral ureteral obstruction(UUO).Methods Forty-four male SD rats were randomly divided into four groups:the sham surgery group(Sham group),the pure drug intervention group(Sham+DHL group),the experimental group(UUO+Vehicle group)and the DHL treatment group(UUO+DHL group),with 11 rats in each group.The rats underwent sham surgery,sham surgery+DHL[10 mg/(kg·d)],UUO modeling+the same volume of solvent and UUO modeling+DHL[10 mg/(kg·d)],respectively.After surgery,DHL or the same volume of solvent was administered by gavage for 14 days starting from day 2 post-surgery.Hematoxylin-eosin(HE)and Masson staining were used to observe the pathological changes in renal tissue.Immunohistochemical staining was performed to detect the expression levels of collagen I,collagen III and α-smooth muscle actin(α-SMA).Western blotting was used to detect the protein levels of the transforming growth factor(TGF)-β1/Smad2/3 pathway.Results Compared with the UUO+Vehicle group,DHL treatment alleviated renal interstitial pathological damage,reduced collagen fiber deposition,and decreased the expression of collagen I,collagen III and α-SMA.It also inhibited the expression of TGF-β1 and Smad2/3 proteins.Conclusions DHL mitigates RIF in rats by inhibiting the TGF-β1/Smad2/3 pathway,providing a new strategy for the treatment of chronic kidney disease.

Background and Aims:Pancreatic cancer(PC)is a highly lethal gastrointestinal malignancy with poorly understood pathogenesis.Previous studies suggest that alterations in plasma metabolomics may be associated with PC development;however,traditional observational studies are prone to confounding and reverse causation,making it difficult to establish causal relationships.This study employed a two-sample Mendelian randomization(MR)approach to systematically evaluate the potential causal relationship between 325 nuclear magnetic resonance(NMR)metabolites and PC risk.Methods:Genome-wide association study(GWAS)data of 325 NMR metabolites from the UK Biobank were integrated with GWAS data of PC from FinnGen.Single nucleotide polymorphisms(SNPs)significantly associated with metabolites were selected as instrumental variables.The inverse variance weighted method served as the primary analysis,supplemented by MR-Egger regression,weighted median,weighted mode,Bayesian weighted Mendelian randomization(BWMR),and constrained maximum likelihood(cML)for validation.Multiple sensitivity analyses were performed to assess the robustness of the results.Results:Four metabolites were identified to have significant causal associations with PC risk.Higher phospholipid-to-total lipid ratios in intermediate-density lipoproteins(IDL)(GCST90445881)and small high density lipoproteins(HDL)(GCST90446027),as well as higher free cholesterol-to-total lipid ratios in extremely large very-low-density lipoproteins(VLDL)(GCST90446151),were inversely associated with PC risk.Conversely,an elevated triglyceride-to-total lipid ratio in chylomicrons and extremely large VLDL(GCST90446157)was positively associated with increased PC risk.The findings were consistently supported by multiple sensitivity analyses.Conclusion:This study provides genetic evidence linking lipid metabolism alterations to PC risk.Elevated phospholipid and free cholesterol ratios appear protective,whereas increased triglyceride levels act as risk factors.These metabolite profiles may serve as promising biomarkers for early diagnosis and intervention in PC,offering novel insights for risk assessment and potential metabolic-targeted therapies.

Pancreatic cancer is highly aggressive and often diagnosed at an advanced stage,leaving most patients ineligible for radical resection.This study retrospectively analyzed four patients with locally advanced or advanced pancreatic cancer to evaluate the clinical efficacy and safety of high-intensity focused ultrasound(HIFU)ablation combined with chemotherapy as a neoadjuvant and conversion therapy.All cases were reviewed and individualized treatment plans were formulated through a multidisciplinary team evaluation.All patients received HIFU plus gemcitabine and nab-paclitaxel chemotherapy,with assessments of tumor volume,vascular involvement,surgical conversion,symptom relief,and adverse events.Three patients achieved marked tumor shrinkage and reduction of vascular invasion,enabling successful R0 resection without recurrence during follow-up.The remaining patient achieved disease stability,significant pain relief,and maintained good quality of life under repeated HIFU therapy.All treatments were well tolerated,and no severe adverse reactions occurred.The combination of HIFU and chemotherapy demonstrated synergistic local and systemic effects,effectively achieving tumor downstaging,improving resectability,and alleviating symptoms.As a safe,noninvasive,and repeatable therapeutic approach,this strategy offers a promising option for patients with advanced pancreatic cancer.Further large-scale prospective studies are warranted to validate its long-term efficacy and elucidate underlying mechanisms.

Pancreatic cancer is highly aggressive and often diagnosed at an advanced stage,leaving most patients ineligible for radical resection.This study retrospectively analyzed four patients with locally advanced or advanced pancreatic cancer to evaluate the clinical efficacy and safety of high-intensity focused ultrasound(HIFU)ablation combined with chemotherapy as a neoadjuvant and conversion therapy.All cases were reviewed and individualized treatment plans were formulated through a multidisciplinary team evaluation.All patients received HIFU plus gemcitabine and nab-paclitaxel chemotherapy,with assessments of tumor volume,vascular involvement,surgical conversion,symptom relief,and adverse events.Three patients achieved marked tumor shrinkage and reduction of vascular invasion,enabling successful R0 resection without recurrence during follow-up.The remaining patient achieved disease stability,significant pain relief,and maintained good quality of life under repeated HIFU therapy.All treatments were well tolerated,and no severe adverse reactions occurred.The combination of HIFU and chemotherapy demonstrated synergistic local and systemic effects,effectively achieving tumor downstaging,improving resectability,and alleviating symptoms.As a safe,noninvasive,and repeatable therapeutic approach,this strategy offers a promising option for patients with advanced pancreatic cancer.Further large-scale prospective studies are warranted to validate its long-term efficacy and elucidate underlying mechanisms.

Objective To analyze the clinical value of fungus(1,3)-β-D glucan test magnetic particle chemiluminescence immunoas-say(G-CLIA)for diagnosis of invasive fungal disease(IFD).Methods A total of 509 patients with clinically suspected IFD in Qilu Hospital of Shandong University from 1 March to 30 April,2023 were collected.According to the inclusion criteria,the 509 patients were grouped into IFD group(141 patients)and non-IFD group(368 patients).The sensitivity,specificity,accuracy,positive predic-tive value and negative predictive value of G-CLIA were analyzed,and the consistency of the results of G-CLIA with G test colorimetric method,fungal smear microscopy or culture and metagenomics next-generation sequencing(mNGS)was comparatively analyzed.Re-sults The sensitivity and specificity of G-CLIA were 88.65％and 96.47％,respectively,and the positive percentage agreement of G-CLIA with G test colorimetric assay,fungal smear microscopy or culture,and mNGS were 92.19％,75.86％,and 75.00％,respective-ly,and the consistency of G-CLIA with G test colorimetric assay was the highest(kappa value≥ 0.75).Conclusion G-CLIA has high sensitivity and specificity for detecting IFD with excellent diagnostic value.Combined with the fully automated chemiluminescence analy-zer,G-CLIA test is fast and has a high throughput,which provides a new option for the clinical diagnosis of IFD.

Objective:To investigate the clinical characteristics of urea cycle disorder (UCD), the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy in pediatric patients with UCD.Methods:This study was a retrospective, single-arm, multicenter clinical study. The clinical data of 20 pediatric patients with UCD who received GPB treatment at 9 hospitals nationwide between December 2021 and August 2024 were collected. The clinical manifestations, laboratory results, and molecular genetic characteristics were analyzed, ammonia levels and other laboratory results were evaluated pre-post GPB therapy by paired t-tests or Wilcoxon tests. Results:Among the 20 pediatric patients with UCD, there were 8 males and 12 females, and the onset age was 2.8 (1.4, 5.7) years. The ammonia levels were 174 (125, 342) μmol/L at first onset. The symptoms included vomiting in 6 cases, drowsiness in 5 cases, epilepsy in 5 cases, developmental delay in 5 cases, psychiatric and behavioral abnormalities in 3 cases, and lethargy in 1 case, and 18 cases exhibited abnormal liver function. Twenty cases included 6 UCD subtypes, with 11 cases being ornithine transcarbamylase deficiency. A total of 27 variants were identified, 11 (41%) of which were novel. The age of patients who began GPB therapy was 4.0 (1.5, 6.6) years. Ten cases stopped GPB after 4.2 (3.4, 5.3) months, with 4 patients undergoing liver transplantation and 6 discontinuing for financial reasons. The remaining ten patients continued GPB therapy for 11.6 (8.6, 14.0) months. The duration of GPB treatment was 6.0 (4.2, 12.3) months, at the final visit, the levels of ammonia, platelets and aspartate aminotransferase were lower compared to those of pre-treatment (all P<0.05). The serum albumin level was higher than that of pre-treatment ( P=0.016). Two patients suffered only one episode of acute hyperammonaemia, with ammonia levels of 232 and 141 μmol/L, respectively. Nine cases experienced adverse effects potentially related to GPB, decreased appetite in 6 cases, vomiting in 3 cases, abnormal skin oil odor in 2 cases, somnolence, fatigue and diarrhea each in 1 case, with symptoms improved within 6 (3, 10) days. Conclusions:UCD primarily manifests with neurological and gastrointestinal symptoms, and early diagnosis of UCD could be achieved through the analysis of ammonia. GPB may effectively reduce ammonia levels in UCD pediatric patients, with favorable safety and tolerability.

Objective To understand the situation of dental cone beam computed tomography (CBCT) quality control testing phantoms in radiation health technical service institutions in Guangdong province, analyze the differences among different phantoms, and provide a reference for dental CBCT quality control testing. Methods The testing phantoms of 49 radiation health technical service institutions were used as the research objects. The designated CBCT equipment was used for scanning and imaging. The Z-score method was used to evaluate the high-contrast resolution, low-contrast resolution, and distance measurement deviation of each phantom. Results The satisfaction rates of various items for the phantoms in 49 institutions ranged from 85.7% to 100%. The distance measurement deviations of four institutions were “suspicious”, and the high-contrast resolution of four institutions and the distance measurement deviation of one institution were “unsatisfactory”. Conclusion The overall performance of dental CBCT quality control testing phantoms in radiological health technical service institutions in Guangdong province is satisfactory. However, there are still some phantoms with poor results in items such as distance measurement deviation and high-contrast resolution. The structural design, material selection, and manufacturing process of the phantom may all affect the results of quality control testing. Therefore, appropriate phantoms, optimized exposure conditions, and suitable reconstruction algorithms should be used in CBCT quality control testing to ensure accurate and reliable measurements.

The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery. In this study, by screening fungal extracts against coxsackievirus B3 (CVB3), three new aspochalasins, templichalasins A‒C (1‒3), along with six known aspochalasins (4‒9) were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045. Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system, while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons. Their structures were characterized through extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Additionally, we demonstrated that compound 4 can be readily converted into compounds 1‒3 under mild acidic conditions and proposed a plausible mechanism for this conversion. Bioactivity evaluation of compounds 1‒9 against CVB3 revealed the inhibitory effects of all compounds against the virus. Notably, compound 9 exhibited superior antiviral activity, surpassing the commercial drug ribavirin in selectivity index (SI) value.
Antiviral Agents/isolation & purification* ; Aspergillus/chemistry* ; Molecular Structure ; Enterovirus B, Human/drug effects* ; Endophytes/chemistry* ; Cytochalasins/isolation & purification* ; Drug Discovery ; Humans

In recent years, with continuous advancements in molecular biology and gene testing technologies, the diagnosis and treatment of colorectal cancer have been rapidly transitioning toward precision medicine. The application of molecular classification, target detection, and liquid biopsy technologies has driven ongoing updates to clinical guidelines. Multidisciplinary team colla-boration, innovations in precision surgical techniques, and the widespread adoption of neoadjuvant combination therapies have collectively promoted more individualized and scientific management of colorectal cancer. Looking ahead,the authors believe that as multi-omics biomarkers, organoid models, and artificial intelligence are increasingly integrated into clinical practice, precision diagnosis and treatment of colorectal cancer will deepen further, offering patients more efficient and personalized therapeutic options.

Objective:To analyze the clinical characteristics of locally advanced rectal cancer patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy combined with immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 46 patients with locally advanced rectal cancer who were admitted to 6 medical centers, including Beijing Friendship Hospital of Capital Medical University et al, from June 2021 to November 2022 were collected. There were 29 males and 17 females, aged (61±4)years. Patients received neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitor therapy, and under-went radical total mesorectal excision during 6-12 weeks after radiotherapy. Observation indicators: (1) comparison of clinical characteristics between pCR and non-pCR patients;(2) postoperative complications and adverse reactions of pCR and non-pCR patients. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. Results:(1) Comparison of clinical characteristics between pCR and non-pCR patients. Before neoadjuvant therapy, there were 14 cases aged ≥50 years and 6 cases aged <50 years in pCR patients, versus 25 cases and 1 case in non-pCR patients, showing a significant difference between the two groups ( P<0.05). After neoadjuvant therapy, cases in clinical stage T0, T1, T2, T3, T4 were 11, 1, 5, 3, 0 for pCR patients versus 7, 4, 2, 11, 2 for non-pCR patients, cases of tumor regression grade 1, 2, 3, 4 were 11, 8, 1, 0 for pCR patients versus 7, 14, 4, 1 for non-pCR patients, cases in low-risk, medium-risk, high-risk of neoadjuvant rectal scoring and grading were 20, 0, 0 for pCR patients versus 4, 18, 4 for non-pCR patients, respectively, showing significant differences in above indicators between the two groups ( Z=-2.256, -2.104, -5.458, P<0.05). (2) Postoperative complications and adverse reactions of pCR and non-pCR patients. Postoperative complications occurred in 2 cases of pCR patients and 5 cases of non-pCR patients, postoperative adverse reactions occurred in 11 cases of pCR patients and 10 cases of non-pCR patients, showing no significant difference between the two groups ( P>0.05). Conclusion:Compared with locally advanced rectal cancer patients aged ≥50 years, those aged <50 years have significant benefits from neoadjuvant chemoradiotherapy combined with immunotherapy. Clinical T staging and magnetic resonance imaging-detected tumor regression grade after neoadjuvant therapy have predictive value for patients with pCR .