This study aimed to investigate the effect of saltwater stir-fried Plantaginis Semen(SPS) on renal fibrosis in rats and decipher the underlying mechanism. Thirty-six Sprague-Dawley rats were randomly assigned into control, model, losartan potassium, and low-, medium-, and high-dose(15, 30, and 60 g·kg~(-1), respectively) SPS groups. Rats in other groups except the control group were subjected to unilateral ureteral obstruction(UUO) to induce renal fibrosis, and the modeling and gavage lasted for 14 days. After 14 consecutive days of treatment, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in rats of each group were determined by an automatic biochemical analyzer. Hematoxylin-eosin(HE) and Masson staining were used to evaluate pathological changes in the renal tissue. Western blot and immunofluorescence assay were conducted to determine the protein levels of fibronectin(FN), collagen Ⅰ, vimentin, and α-smooth muscle actin(α-SMA) in the renal tissue. The mRNA levels of epithelial-mesenchymal transition(EMT)-associated transcription factors including twist family bHLH transcription factor 1(TWIST1), snail family transcriptional repressor 1(SNAI1), and zinc finger E-box binding homeobox 1(ZEB1), as well as inflammatory cytokines such as interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), were determined by RT-qPCR. Human renal proximal tubular epithelial(HK2) cells exposed to transforming growth factor-β(TGF-β) for the modeling of renal fibrosis were used to investigate the inhibitory effect of SPS on EMT. Network pharmacology and Western blot were employed to explore the molecular mechanism of SPS in alleviating renal fibrosis. The results showed that SPS significantly reduced Scr and BUN levels and alleviated renal injury and collagen deposition in UUO rats. Moreover, SPS notably down-regulated the protein levels of FN, collagen Ⅰ, vimentin, and α-SMA as well as the mRNA levels of SNAI1, ZEB1, TWIST1, IL-1β, IL-6, and TNF-α in the kidneys of UUO rats and TGF-β-treated HK-2 cells. In addition, compared with Plantaginis Semen without stir-frying with saltwater, SPS showed increased content of specific compounds, which were mainly enriched in the mitogen-activated protein kinase(MAPK) signaling pathway. SPS significantly inhibited the phosphorylation of extracellular signal-regulated kinase(ERK) and p38 MAPK in the kidneys of UUO rats and TGF-β-treated HK2 cells. In conclusion, SPS can alleviate renal fibrosis by attenuating EMT through inhibition of the MAPK signaling pathway.
Animals ; Epithelial-Mesenchymal Transition/drug effects* ; Rats, Sprague-Dawley ; Male ; Rats ; Fibrosis/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Kidney Diseases/pathology* ; Kidney Tubules/pathology* ; Humans

This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

OBJECTIVE: To investigate the early clinical efficacy of single-position O-arm navigation-assisted oblique lateral interbody fusion(OLIF) combined with minimally invasive percutaneous pedicle screw fixation(PPS) in the treatment of lumbar spondylolisthesis. METHODS: A retrospective analysis was conducted on 22 patients with lumbar spondylolisthesis who underwent OLIF-PPS surgery including 11 males and 11 females with a mean age of (64.6±1.5) years old ranging from 49 to 80 years old between April 2021 and June 2023. All patients presented with lumbosacral pain, lower limb radiating pain, numbness, and had poor responses to conservative treatment. Surgical time, intraoperative blood loss, hospital stay, and postoperative complications were recorded. Clinical outcomes were evaluated using the visual analogue scale(VAS) and Oswestry disability index(ODI) preoperatively at 3 days after operation and the final follow-up. Standing lumbar anteroposterior and lateral X-rays were performed to measure disc height(DH), slippage degree, vertebral reduction rate, pedicle screw accuracy, and cage subsidence. RESULTS: All surgeries were successfully completed with a mean follow-up of (27.1±2.2) months (range 18 to 36 months). The mean surgical time was (76.1±12.2) min (range 60 to 93 min), intraoperative blood loss was (86.3±32.2) ml (range 40 to 113 ml), and hospital stay was (7.1±1.2) days. Postoperative VAS significantly improved from (7.2±0.7) preoperatively to (2.3±0.5) at 3 days after operation and (1.7±0.2) at the final follow-up (P<0.05). ODI decreased from (68.5±7.2)% preoperatively to (30.3±3.1)% at 3 days after operation and (16.6±1.6)% at the final follow-up (P<0.05). DH increased from (8.5±1.7) mm preoperatively to (18.1±1.4) mm at 3 days after operation and (17.2±1.1) mm at the final follow-up (P<0.05). Slippage degree improved from (24.1±4.6)% preoperatively to (10.3±4.2)% at 3 days after operation and (10.1±3.2)% at the final follow-up (P<0.05). A total of 88 pedicle screws were implanted with an excellent rate of 98% (86/88). Complications included transient left hip flexion weakness (2 cases) and left anteromedial thigh pain (1 case), all resolved during follow-up. No incision hematoma, infection, screw loosening, or cage subsidence occurred. CONCLUSION Single-position O-arm navigation-assisted OLIF combined with PPS demonstrates satisfactory early clinical efficacy for lumbar spondylolisthesis, with advantages including minimal invasiveness, significant pain relief, effective vertebral reduction, and low complication rates.
Humans ; Male ; Female ; Spondylolisthesis/diagnostic imaging* ; Middle Aged ; Aged ; Spinal Fusion/methods* ; Lumbar Vertebrae/diagnostic imaging* ; Minimally Invasive Surgical Procedures/methods* ; Pedicle Screws ; Aged, 80 and over ; Retrospective Studies

Traditional Chinese medicine (TCM) represents a paradigmatic approach to personalized medicine, developed through the systematic accumulation and refinement of clinical empirical data over more than 2000 years, and now encompasses large-scale electronic medical records (EMR) and experimental molecular data. Artificial intelligence (AI) has demonstrated its utility in medicine through the development of various expert systems (e.g., MYCIN) since the 1970s. With the emergence of deep learning and large language models (LLMs), AI's potential in medicine shows considerable promise. Consequently, the integration of AI and TCM from both clinical and scientific perspectives presents a fundamental and promising research direction. This survey provides an insightful overview of TCM AI research, summarizing related research tasks from three perspectives: systems-level biological mechanism elucidation, real-world clinical evidence inference, and personalized clinical decision support. The review highlights representative AI methodologies alongside their applications in both TCM scientific inquiry and clinical practice. To critically assess the current state of the field, this work identifies major challenges and opportunities that constrain the development of robust research capabilities-particularly in the mechanistic understanding of TCM syndromes and herbal formulations, novel drug discovery, and the delivery of high-quality, patient-centered clinical care. The findings underscore that future advancements in AI-driven TCM research will rely on the development of high-quality, large-scale data repositories; the construction of comprehensive and domain-specific knowledge graphs (KGs); deeper insights into the biological mechanisms underpinning clinical efficacy; rigorous causal inference frameworks; and intelligent, personalized decision support systems.
Medicine, Chinese Traditional/methods* ; Artificial Intelligence ; Humans ; Precision Medicine ; Decision Support Systems, Clinical

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

OBJECTIVE: Asthma imposes a significant global health burden. This study examines changes in the asthma-related disease burden from 1990 to 2021 and projects future burdens for 2050 under different scenarios. METHODS: Using data from the Global Burden of Disease 2021 study, we analyzed asthma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. We projected the disease burden for 2050 based on current trends and hypothetical scenarios in which all risk factors are controlled. Temporal trends in age-standardized incidence, prevalence, mortality, and DALY rates were explored using Annual Percent Change. RESULTS: In 2021, the age-standardized rates for asthma incidence, prevalence, mortality, and DALYs in China were 364.17 per 100,000 (95% uncertainty interval [ UI]: 283.22-494.10), 1,956.49 per 100,000 (95% UI: 1,566.68-2,491.87), 1.47 per 100,000 (95% UI: 1.15-1.79), and 103.76 per 100,000 (95% UI: 72.50-145.46), respectively. A higher disease burden was observed among Chinese men and individuals aged 70 years or older. Compared to the current trend, a combined scenario involving improvements in environmental factors, behavioral and metabolic health, child nutrition, and vaccination resulted in a greater reduction in the disease burden caused by asthma. CONCLUSION Addressing modifiable risk factors is essential for further reducing the asthma-related disease burden.
Humans ; Asthma/mortality* ; China/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Aged ; Child ; Adolescent ; Global Burden of Disease/trends* ; Child, Preschool ; Young Adult ; Infant ; Cost of Illness ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Infant, Newborn ; Aged, 80 and over ; Risk Factors

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective:To construct and evaluate a radiomics model for predicting perineural invasion in patients with intrahepatic cholangiocarcinoma (ICC).Methods:Clinical data of 144 patients with ICC undergoing surgery in the People’s Hospital of Zhengzhou University ( n=113) and the Affiliated Cancer Hospital of Zhengzhou University ( n=31) from January 2018 to June 2023 were retrospectively analyzed, including 80 males and 64 females, aged (58.8±10.1) years. The patients were randomly divided into a training set ( n=100) and a test set ( n=44) at a ratio of 7: 3. The former set was used to build the model for predicting perineural invasion, and the latter was used to evaluate the model. Enhanced CT images and clinical data of the patients were collected, and features related to perineural invasion were screened. A light gradient boosting machine was used to construct an imaging genomics model. The model was evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results:Univariate and multivariate logistic regression analysis showed that none of the clinical features were associated with neural invasion in ICC patients (all P>0.05). Six, 25, 32, and 37 radiomics features were obtained by screening the intratumoral, 2 mm peritumoral, 5 mm peritumoral, and 8 mm peritumoral regions, respectively. The area under the ROC curve for predicting perineural invasion in ICC patients was 0.849 (95% CI: 0.774-0.923) in the training set and 0.745 (95% CI: 0.597-0.894) in the test set for the intratumoral model, 0.966 (95% CI: 0.938-0.995) and 0.750 (95% CI: 0.604-0.896) for the 5mm peritumoral model, 0.936 (95% CI: 0.892-0.980) and 0.792 (95% CI: 0.644-0.939) for the 2mm peritumoral model, and 0.961 (95% CI: 0.929-0.992) and 0.689 (95% CI: 0.526-0.853) for the 8mm peritumoral model. The area under the ROC curve, accuracy, sensitivity, and specificity of the combined intratumoral and 5mm peritumoral model for predicting perineural invasion were 0.927 (95% CI: 0.878-0.976), 88.0%, 84.5%, and 89.8% in the training set, and 0.849 (95% CI: 0.737-0.960), 77.3%, 85.2%, and 72.0% in the test set, respectively. The calibration curve showed a deviation between the calibration curve of the combined intratumoral and 5mm peritumoral model and the ideal line, but it could achieve basic consistency. DCA showed that when the threshold was between 0.18 and 0.70, the combined intratumoral and 5mm peritumoral model could bring clinical net benefit to patients when predicting neural invasion. Conclusion:The intratumoral and 5mm peritumoral imaging genomics model based on enhanced CT features can effectively predict neural invasion and offer clinical benefits in patients with ICC.