Digestive system malignant tumors （DT） are one of the leading causes of death globally and carry a heavy economic burden. Gut microbiota plays a critical role in maintaining host health， including providing nutrition， defending against pathogens， and promoting immune development. In recent years， more and more studies have shown that dysbiosis of gut microbiota is closely associated with DT such as gastric cancer， liver cancer， and colon cancer. Therefore， targeted regulation of gut microbiota plays a potential role in inhibiting the growth and metastasis of DT， while its specific regulatory mechanism remains unclear. As the studies about the anti-tumor effects of traditional Chinese medicine （TCM）， especially the basic and clinical studies on the regulation of gut microbiota by TCM in tumor treatment， have been growing， the therapeutic effects of TCM on DT have attracted much attention. This paper provides a systematic review of the relationship between gut microbiota and DT， as well as the related studies on the modulation of gut microbiota by TCM against DT， with the aim of providing a foundation and direction for future basic and clinical studies on DT. The literature review shows that gut microbiota influence the occurrence and development of DT through multiple pathways. These pathways include triggering chronic inflammation， producing oncogenic metabolites， inducing genomic instability， regulating the immune system， and altering the tumor microenvironment. TCM can exert anti-DT effects by regulating the composition of gut microbiota， modulating gut microbiota metabolites， repairing intestinal barrier function， and influencing immune functions. Therefore， understanding the relationship between gut microbiota and DT and the regulatory mechanisms of TCM may provide new strategies for future prevention and treatment of DT.

Objective To explore the injury types,associated injuries,and correlations of the lateral meniscus posterior root(LMPR),and to improve the comprehensive understanding of LMPR and its associated injuries.Methods The patients with LMPR who underwent knee MRI examination were retrospectively selected.A total of 223 patients with LMPR injury were classified into 4 types.The integ-rity of the meniscofemoral ligament and the grading of the cartilage injuries in the lateral tibiofemoral compartment were recorded.The relationship between the types of LMPR injury and the lateral meniscus tear locations,as well as lateral meniscus extrusion were analyzed.The relationship between the integrity of the meniscofemoral ligament and lateral meniscus extrusion was analyzed.The correlation between the time to clinical presentation after injury and the grading of the cartilage injuries was analyzed in patients with anterior cruciate ligament(ACL)ruptures.Results The incidence of LMPR injury was 1.02％,with males affected 2.19 times more frequently than females.Among patients with ACL ruptures,the incidence was 13.17％.Both type Ⅰ and type Ⅱ LMPR inju-ries predominantly involved only the posterior root,while type Ⅲ injuries mainly affected the posterior root extending to the posterior horn and body.The incidence of the lateral meniscus extrusion was higher in type Ⅲ LMPR injury than in type Ⅱ.When the menis-cofemoral ligament was not intact,the incidence of the lateral meniscus extrusion increased.In patients with ACL ruptures,a longer time to clinical presentation after injury was associated with more severe cartilage injuries grading in the lateral tibiofemoral compart-ment.Conclusion Males are more susceptible to LMPR injuries than females.The classification of LMPR injuries is correlated with the location of the lateral meniscus tears and the incidence of the lateral meniscus extrusion.The integrity of the meniscofemoral lig-ament is related to the incidence of the lateral meniscus extrusion.The time to clinical presentation after injury is related to the sever-ity of cartilage injury in ACL rupture patients.

Caspase-8 is a cysteine-aspartate protease widely dis-tributed in cells.As a molecular"switch",caspase-8 is involved in the regulation of various modes of cell death,including apopto-sis,necroptosis and pyroptosis.During cerebral ischemia/reper-fusion,caspase-8 activation is one of the key factors inducing neuronal cell death.Currently there are both specific inhibitors of caspase-8,such as Z-IETD-FMK and Ac-IETD-CHO,as well as a variety of pan-caspase inhibitors,such as z-VAD,Q-VD-OPH,and enricosan.Both animal and cellular experiments have demonstrated that all of these inhibitors attenuate cerebral ische-mia/reperfusion injury,an effect that involves inhibition of caspase-8 activity and reduction of neuronal apoptosis.Clinical-ly,certain drugs for ischemic stroke reduce plasma caspase-8 ac-tivity,suggesting that caspase-8 may be a biomarker for the diag-nosis and prognosis of ischemic stroke.Finding and developing clinically valuable inhibitors around caspase-8 is expected to provide new ideas for new drug development in ischemic stroke.

Portal vein thrombosis(PVT)is a common and severe complication in patients with liver cirrhosis,and alterations in portal hemodynamics are closely associated with the development of PVT.The presence of large spontaneous splenorenal shunt(SSRS)may lead to reductions in portal vein perfusion and blood flow velocity,which may compromise the anticoagulant effect on PVT.This article reports the treatment strategies of SSRS embolization combined with anticoagulant therapy that help to achieve complete recanalization of the portal vein;however,high-quality clinical studies are still needed to further validate and support the effectiveness of this strategy.

Portal vein thrombosis(PVT)is a common and severe complication in patients with liver cirrhosis,and alterations in portal hemodynamics are closely associated with the development of PVT.The presence of large spontaneous splenorenal shunt(SSRS)may lead to reductions in portal vein perfusion and blood flow velocity,which may compromise the anticoagulant effect on PVT.This article reports the treatment strategies of SSRS embolization combined with anticoagulant therapy that help to achieve complete recanalization of the portal vein;however,high-quality clinical studies are still needed to further validate and support the effectiveness of this strategy.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To investigate the differences in hippocampal subfield volumes and structural covariance network between participants with subjective cognitive decline (SCD) and healthy individuals, and to analyze the correlations of the volumes of the different subfields and altered covariance brain regions with memory function.Methods:A total of 57 SCD individuals(SCD group) and 44 normal controls(NC group) participants were assessed for memory function using composite scores from the auditory verbal learning test (AVLT) and the Wechsler memory scale visual reproduction (VR) test from June 2022 to October 2023.T1-weighted structural magnetic resonance imaging (MRI) data were collected from all participants, and hippocampal subfields, cortical regions, and subcortical nuclei were segmented using FreeSurfer to measure the gray matter volume of each structure. A structural covariance network was constructed based on the correlation of gray matter volumes across regions. Statistical analysis was performed using R 4.3.1 software. Inter-group differences in hippocampal subfield volumes were compared using multivariate analysis of covariance. Differences in structural covariance connectivity between groups were assessed using Z-test, while network topology differences were compared through permutation testing. Finally, partial correlation analysis was used to examine correlation of the volumes of the differential hippocampal subfields and covariance brain regions with memory function. Results:The SCD group exhibited significantly lower years of education, AVLT-immediate score, AVLT-delayed score, VR-immediate score, VR-delayed score, and memory function Z-score compared to the NC group ( t=2.064, 3.888, 2.622, 3.222, 4.761, 5.184, all P<0.05). The volumes of the right subiculum((387.75±55.20)mm 3, (352.70±70.25)mm 3), left presubiculum((263.12±38.52)mm 3, (239.79±46.02)mm 3), left subiculum((388.12±49.34)mm 3, (351.74±67.30)mm 3) and left CA1((571.01±80.01)mm 3, (526.51±98.80)mm 3) in the SCD group were smaller than the corresponding volumes in NC group ( F=9.139, 8.039, 11.207, 7.266, all P<0.05, FDR correction). Differences in structural covariance connectivity were found between the SCD and NC groups in the following pairs: right CA1-right subiculum, right CA1-left subiculum, right CA3-left parasubiculum and right hippocampus-amygdala transition area-left subiculum ( Z=-3.848, -3.896, -3.597, -3.895, all P<0.05, FDR correction).Partial correlation analysis revealed that in the SCD group, the volume of the left subiculum ( r=0.359, P=0.007), left CA1 ( r=0.430, P=0.001), right entorhinal cortex ( r=0.296, P=0.029), right middle temporal gyrus ( r=0.361, P=0.007), right parahippocampal gyrus ( r=0.313, P=0.021)were positively correlated with the total memory function score. Conclusion:Hippocampal subfields atrophy, as well as alterations in structural covariance network, have been found in SCD individuals. Furthermore, the decline in memory function may be closely associated with atrophy in hippocampal subfields and structurally covariant regions.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To investigate the differences in hippocampal subfield volumes and structural covariance network between participants with subjective cognitive decline (SCD) and healthy individuals, and to analyze the correlations of the volumes of the different subfields and altered covariance brain regions with memory function.Methods:A total of 57 SCD individuals(SCD group) and 44 normal controls(NC group) participants were assessed for memory function using composite scores from the auditory verbal learning test (AVLT) and the Wechsler memory scale visual reproduction (VR) test from June 2022 to October 2023.T1-weighted structural magnetic resonance imaging (MRI) data were collected from all participants, and hippocampal subfields, cortical regions, and subcortical nuclei were segmented using FreeSurfer to measure the gray matter volume of each structure. A structural covariance network was constructed based on the correlation of gray matter volumes across regions. Statistical analysis was performed using R 4.3.1 software. Inter-group differences in hippocampal subfield volumes were compared using multivariate analysis of covariance. Differences in structural covariance connectivity between groups were assessed using Z-test, while network topology differences were compared through permutation testing. Finally, partial correlation analysis was used to examine correlation of the volumes of the differential hippocampal subfields and covariance brain regions with memory function. Results:The SCD group exhibited significantly lower years of education, AVLT-immediate score, AVLT-delayed score, VR-immediate score, VR-delayed score, and memory function Z-score compared to the NC group ( t=2.064, 3.888, 2.622, 3.222, 4.761, 5.184, all P<0.05). The volumes of the right subiculum((387.75±55.20)mm 3, (352.70±70.25)mm 3), left presubiculum((263.12±38.52)mm 3, (239.79±46.02)mm 3), left subiculum((388.12±49.34)mm 3, (351.74±67.30)mm 3) and left CA1((571.01±80.01)mm 3, (526.51±98.80)mm 3) in the SCD group were smaller than the corresponding volumes in NC group ( F=9.139, 8.039, 11.207, 7.266, all P<0.05, FDR correction). Differences in structural covariance connectivity were found between the SCD and NC groups in the following pairs: right CA1-right subiculum, right CA1-left subiculum, right CA3-left parasubiculum and right hippocampus-amygdala transition area-left subiculum ( Z=-3.848, -3.896, -3.597, -3.895, all P<0.05, FDR correction).Partial correlation analysis revealed that in the SCD group, the volume of the left subiculum ( r=0.359, P=0.007), left CA1 ( r=0.430, P=0.001), right entorhinal cortex ( r=0.296, P=0.029), right middle temporal gyrus ( r=0.361, P=0.007), right parahippocampal gyrus ( r=0.313, P=0.021)were positively correlated with the total memory function score. Conclusion:Hippocampal subfields atrophy, as well as alterations in structural covariance network, have been found in SCD individuals. Furthermore, the decline in memory function may be closely associated with atrophy in hippocampal subfields and structurally covariant regions.