OBJECTIVE To investigate the mechanism of Huangqin decoction in improving ulcerative colitis （UC） through the gut microbiota-tryptophan metabolism-aryl hydrocarbon receptor （AhR） axis. METHODS Mice were randomly divided into normal group （normal saline）， model group （normal saline）， microbiota depletion-model group （normal saline）， microbiota depletion-Huangqin decoction group （9.1 g/kg， by crude drug， similarly hereinafter）， Huangqin decoction group and mesalazine group （positive control group， 0.4 g/kg）， with 6 mice in each group. Microbiota depletion was achieved by providing free access to a mixed antibiotics for 10 days. The UC model was induced by administering 2.5% dextran sulfate sodium solution for 7 days. After successful modeling， each treatment group received corresponding drugs or normal saline intragastrically once daily for 10 days. After the final administration， body weight change ratio， disease activity index （DAI） score， and colon length were evaluated； colon pathological changes were observed； serum levels of interleukin-6 （IL-6）， IL-10， IL-22， and tumor necrosis factor-α （TNF-α） were measured； the expressions of Occludin， zonula occluden-1 （ZO-1）， and AhR in colon tissue were detected； fecal samples were subjected to high-throughput sequencing to analyze targeted tryptophan metabolomics. RESULTS Compared with the model group， Huangqin decoction group showed reduced infiltration of inflammatory cells in the colon tissue and restoration of the intestinal mucosal structure. Body weight change ratio， colon length， serum content of IL-10， the expressions of Occludin， ZO-1 and AhR in colon tissue and the contents of tryptophan metabolites indole-3-propionic acid （IPA）， N -acetylserotonin （NAS） and indole-3-acetic acid （IAA） were all significantly increased （ P ＜0.05）； DAI score， serum levels of IL-6， TNF-α， and IL-22 and the content of tryptophan metabolite indole-3-ethanol were significantly decreased （ P ＜0.05）； gut microbiota structure was improved， with increased relative abundances of beneficial bacteria such as Lactobacillus ， and decreased relative abundances of pathogenic bacteria such as Escherichia-Shigella . However， after antibiotic-induced microbiota depletion， although Huangqin decoction significantly increased the content of NAS in the feces of mice， the expression of AhR protein in colon tissue did not increase concurrently. CONCLUSIONS Huangqin decoction can repair the intestinal mucosal barrier in UC mice by regulating the gut microbiota and promoting the production of IPA and IAA， thereby activating AhR. This suggests that an intact gut microbiota is an important prerequisite for Huangqin decoction to exert its AhR-regulating effects.

BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.

Objective:To evaluate the effect of fiberoptic endoscopic evaluation of swallowing (FEES) on clinical functional outcomes of patients with intensive care unit-acquired swallowing disorders (ICU-ASD).Methods:This retrospective cohort study analyzed clinical data of patients diagnosed with post-extubation dysphagia (PED) in the intensive care unit (ICU) and respiratory intensive care unit (RICU) of the Affiliated Hospital of Inner Mongolia Medical University from February 2020 to February 2025. Patients were categorized into a FEES group of 60 cases [34 males, 26 females, aged 37-80 years (median age 62 years)] and a control group without FEES of 58 cases [32 males, 26 females, aged 39-77 years (median age 61 years)].The patients in two groups received swallowing function and feeding training based on the results of the FEES assessment and the Volume-Viscosity Swallow Test-Clinical Version (VVST-CV), respectively. Clinical functional outcome measures included pneumonia incidence, clinical pulmonary infection score (CPIS), pneumonia severity index (PSI), Functional Oral Intake Scale (FOIS), and dietary method at discharge. χ2 test, Mann-Whitney U test, and Wilcoxon signed-rank test, were employed for statistical analysis of the outcome measures. Results:Compared with the control group, the FEES group had significantly lower aspiration pneumonia incidence at discharge [3.3% (2/60) vs 15.5% (9/58), χ2=5.179, P=0.023]. Regarding dietary methods,a significantly higher proportion of patients in the FEES group achieved complete oral feeding compared with the control group [75.0% (45/60) vs 67.3% (39/58), χ2=8.065, P<0.05]. After training, the FEES group had higher median FOIS scores than the control group (7.00 vs 6.00, Z=-2.370, P=0.018), and lower CPIS scores (2.50 vs 5.00, Z=-2.216, P=0.027) and PSI scores (59.00 vs 73.00, Z=-2.251, P=0.024). Within-group comparisons revealed that FOIS scores significantly improved post-training in both groups (both P<0.001). Conclusion:Early FEES examination for ICU patients with acquired swallowing disorders is associated with a lower incidence of pneumonia, improved swallowing function, and superior clinical functional outcomes.

Objective:To evaluate the effect of fiberoptic endoscopic evaluation of swallowing (FEES) on clinical functional outcomes of patients with intensive care unit-acquired swallowing disorders (ICU-ASD).Methods:This retrospective cohort study analyzed clinical data of patients diagnosed with post-extubation dysphagia (PED) in the intensive care unit (ICU) and respiratory intensive care unit (RICU) of the Affiliated Hospital of Inner Mongolia Medical University from February 2020 to February 2025. Patients were categorized into a FEES group of 60 cases [34 males, 26 females, aged 37-80 years (median age 62 years)] and a control group without FEES of 58 cases [32 males, 26 females, aged 39-77 years (median age 61 years)].The patients in two groups received swallowing function and feeding training based on the results of the FEES assessment and the Volume-Viscosity Swallow Test-Clinical Version (VVST-CV), respectively. Clinical functional outcome measures included pneumonia incidence, clinical pulmonary infection score (CPIS), pneumonia severity index (PSI), Functional Oral Intake Scale (FOIS), and dietary method at discharge. χ2 test, Mann-Whitney U test, and Wilcoxon signed-rank test, were employed for statistical analysis of the outcome measures. Results:Compared with the control group, the FEES group had significantly lower aspiration pneumonia incidence at discharge [3.3% (2/60) vs 15.5% (9/58), χ2=5.179, P=0.023]. Regarding dietary methods,a significantly higher proportion of patients in the FEES group achieved complete oral feeding compared with the control group [75.0% (45/60) vs 67.3% (39/58), χ2=8.065, P<0.05]. After training, the FEES group had higher median FOIS scores than the control group (7.00 vs 6.00, Z=-2.370, P=0.018), and lower CPIS scores (2.50 vs 5.00, Z=-2.216, P=0.027) and PSI scores (59.00 vs 73.00, Z=-2.251, P=0.024). Within-group comparisons revealed that FOIS scores significantly improved post-training in both groups (both P<0.001). Conclusion:Early FEES examination for ICU patients with acquired swallowing disorders is associated with a lower incidence of pneumonia, improved swallowing function, and superior clinical functional outcomes.

Objective:To observe the changes in choroidal morphology and blood perfusion in patients with macular edema secondary to retinal vein occlusion (RVO) after intravitreal injections of ranibizumab.Methods:A cohort study was performed.A total of 157 patients (157 eyes) with macular edema secondary to monocular acute retinal vein occlusion (RVO) were enrolled in the Third People's Hospital of Dalian from January 2022 to March 2023.There were 66 cases (66 eyes) with central retinal vein occlusion (CRVO) and 91 cases (91 eyes) with branch retinal vein occlusion (BRVO).All patients were treated with 3+ pro re nata (PRN) regimen of ranibizumab.Before and 1 month after each injection, the central retinal thickness of the macula was measured by optical coherence tomography (OCT).Clear images of the choroid were obtained using the OCT enhanced depth scan mode.Subfoveal choroidal thickness (SFCT), the nasal choroidal thickness at 1 500 μm of macula (CT N1.5 mm), the temporal choroidal thickness at 1 500 μm of macula (CT T1.5 mm) were measured and mean macular thickness (CT Mean) was calculated.Binarization of choroidal images processed by ImageJ software was used to analyze luminal area (LA), stromal area (SA) and total choroidal area (TCA), and choroidal vascularity index (CVI) was calculated.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the Third People's Hospital of Dalian (No.2023-145-001).Results:SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA, SA, TCA and CVI of RVO eyes were higher than those of the contralateral eyes and the differences were statistically significant (all P<0.01).CT Mean in CRVO group was (326.99±64.92)μm, which was higher than (299.80±73.08)μm in BRVO group, with a statistically significant difference ( t=2.41, P=0.02).Baseline CVI values in CRVO group and BRVO group were (72.50±5.62)% and (72.33±5.85)%, respectively, with no significant difference ( t=0.187, P=0.85).In eyes with RVO, CRVO and BRVO, SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA, SA, TCA and CVI after every injection were lower than the baseline and the differences were statistically significant (all P<0.05).In eyes with CRVO, there was no significant difference in LA and CVI between first and second injections (both P>0.05), and SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, SA and TCA after second injection were lower than those after first injection with statistically significant differences (all P<0.05).In eyes with BRVO, there was no significant difference in SA and CVI between first and second injections (both P>0.05), and SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA and TCA after second injection were lower than those after first injection with statistically significant differences (all P<0.05).In eyes with RVO, CRVO and BRVO, there was no significant difference in SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, SA, TCA and CVI between second and third injections (all P>0.05). Conclusions:After intravitreal injection of ranibizumab, the choroidal thickness becomes thinner and CVI decreases in eyes with macular edema secondary to RVO, and remain relatively stable after the second injection.

Objective:To observe the changes in choroidal morphology and blood perfusion in patients with macular edema secondary to retinal vein occlusion (RVO) after intravitreal injections of ranibizumab.Methods:A cohort study was performed.A total of 157 patients (157 eyes) with macular edema secondary to monocular acute retinal vein occlusion (RVO) were enrolled in the Third People's Hospital of Dalian from January 2022 to March 2023.There were 66 cases (66 eyes) with central retinal vein occlusion (CRVO) and 91 cases (91 eyes) with branch retinal vein occlusion (BRVO).All patients were treated with 3+ pro re nata (PRN) regimen of ranibizumab.Before and 1 month after each injection, the central retinal thickness of the macula was measured by optical coherence tomography (OCT).Clear images of the choroid were obtained using the OCT enhanced depth scan mode.Subfoveal choroidal thickness (SFCT), the nasal choroidal thickness at 1 500 μm of macula (CT N1.5 mm), the temporal choroidal thickness at 1 500 μm of macula (CT T1.5 mm) were measured and mean macular thickness (CT Mean) was calculated.Binarization of choroidal images processed by ImageJ software was used to analyze luminal area (LA), stromal area (SA) and total choroidal area (TCA), and choroidal vascularity index (CVI) was calculated.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the Third People's Hospital of Dalian (No.2023-145-001).Results:SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA, SA, TCA and CVI of RVO eyes were higher than those of the contralateral eyes and the differences were statistically significant (all P<0.01).CT Mean in CRVO group was (326.99±64.92)μm, which was higher than (299.80±73.08)μm in BRVO group, with a statistically significant difference ( t=2.41, P=0.02).Baseline CVI values in CRVO group and BRVO group were (72.50±5.62)% and (72.33±5.85)%, respectively, with no significant difference ( t=0.187, P=0.85).In eyes with RVO, CRVO and BRVO, SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA, SA, TCA and CVI after every injection were lower than the baseline and the differences were statistically significant (all P<0.05).In eyes with CRVO, there was no significant difference in LA and CVI between first and second injections (both P>0.05), and SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, SA and TCA after second injection were lower than those after first injection with statistically significant differences (all P<0.05).In eyes with BRVO, there was no significant difference in SA and CVI between first and second injections (both P>0.05), and SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA and TCA after second injection were lower than those after first injection with statistically significant differences (all P<0.05).In eyes with RVO, CRVO and BRVO, there was no significant difference in SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, SA, TCA and CVI between second and third injections (all P>0.05). Conclusions:After intravitreal injection of ranibizumab, the choroidal thickness becomes thinner and CVI decreases in eyes with macular edema secondary to RVO, and remain relatively stable after the second injection.

BACKGROUND:The highest incidence of spinal fracture is in the thoracolumbar segment,and its symptoms are back pain,posterior convexity deformity,activity limitation,or with spinal cord nerve injury causing lower limb pain,numbness,and even paraplegia and other complications.The finite element method is a digital computer modeling technique,which can simulate the physical model and carry out force analysis realistically.OBJECTIVE:To review the application of finite element method in thoracolumbar spine fractures.METHODS:We searched the Chinese and English literature databases PubMed,Web of Science,and CNKI for relevant literature on the application of the finite element analysis method in spinal thoracolumbar fracture published before March 2024.The search terms in Chinese and English were:finite element analysis methods,biomechanical phenomena,stress analysis,thoracolumbar fractures,spinal fractures.Finally,55 papers were included.RESULTS AND CONCLUSION:(1)The exploration of thoracolumbar fractures caused by different etiologies(osteoporotic,traumatic,and pathological)through the finite element method is conducive to a deeper understanding of the biomechanics of various types of thoracolumbar fractures,and to improve the individualized and fine-tuned treatment of thoracolumbar fractures.(2)The finite element analysis of a single sample or a small number of samples has the chance,and a larger number of samples are required for the future finite element analysis to reduce the chance caused by the sample.(3)The rigid structure of bones alone cannot meet the biomechanical working conditions of the integrity of the physical object,and future finite element models need to incorporate all the structures of the physical object(e.g.,soft tissues,such as muscles and ligaments)as far as possible.(4)The finite element method has been used in more studies on osteoporotic and traumatic thoracolumbar spine fractures,which will need to be more in-depth in the future,and less in the field of pathologic thoracolumbar fractures,which has a wider scope for future research.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To develop a convolutional neural network model of whole slide imaging of cerebrospinal fluid cells for rapid and accurate identification and classification of tumor cells in cerebrospinal fluid.Methods:A total of 8 692 cerebrospinal fluid cytology smears from Huashan Hospital Affiliated to Fudan University from January 2nd, 2019, to December 27th, 2024. As randomly assigned, the training set included 4 941 benign and 1 745 malignant samples, while the validation set comprised of 1 368 benign and 638 malignant samples. Whole-slide digital images were acquired using a cytopathology scanner, cells (clusters) were annotated for classification, and a deep learning model was constructed via tiled image patches for cell detection and classification. Model performance was evaluated using accuracy, sensitivity, specificity, and other indicators. The classification efficiency of manual microscopy was compared.Results:The model achieved a mean precision of 96.75% for cerebrospinal fluid cell classification. For malignant tumor cells, the classification accuracy was 96.61% (mAP=98.36%, AUC=0.97). Subtype classification accuracies for epithelial/epithelioid tumors and small round cell tumors were 97.13% (AUC=0.98) and 95.58% (AUC=0.93), respectively. Compared with manual microscopy, which took (9.70±0.82) minutes for classifying 200 cells, (18.27±1.21) minutes for 500 cells, and often exceeded 60 minutes or infeasible for full slides, the AI model took (3.46±0.49) seconds for 200 cells, (6.76±0.82) seconds for 500 cells, and a median of 48.57 seconds for full slides ( P<0.001), representing an efficiency improvement of approximately 161-170 times, significantly enhancing diagnostic efficiency. Conclusion:This fully automated hierarchical deep learning model enables efficient and accurate tumor cell identification and classification in CSF, providing an effective auxiliary tool for the rapid diagnosis of meningeal carcinomatosis.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.