Purpose To explore the changes of brain function and network in primary insomnia(PI)patients using the percent amplitude of fluctuation(perAF)combined with functional connectivity(FC).Materials and Methods A total of 51 PI patients and 45 normal controls underwent resting functional magnetic resonance scans in Kunshan Traditional Chinese Medicine Hospital from November 2019 to December 2022,then the perAF value and FC in brain regions of different perAF value between the two groups was analyzed.Pearson correlation analysis was used to investigate the relationships between the altered perAF values and insomnia years,Pittsburgh sleep quality index and Montreal cognitive assessment.Results Compared with healthy group,PI patients had increased perAF values in the left prefrontal lobe(-42 9 45)and decreased perAF values in the right parahippocampal gyrus(27-12-27)[Gaussian random field(GRF)correction,voxel-wise P<0.001,cluster-level P<0.05].FC analysis showed that the right parahippocampal gyrus of PI patients exhibited significantly increased FC with the left middle temporal gyrus,inferior temporal gyrus(-57-15-33)and the left middle occipital gyrus(-30-78 27)(GRF corrected,voxel-wise P<0.001,cluster-level P<0.05).It was noteworthy that the perAF values of the right parahippocampal gyrus were positively correlated with Montreal cognitive assessment of PI patients(r=0.428,P=0.002).Conclusion Specific brain areas in PI patients may exhibit aberrant neuronal activity,mainly manifested as decreased perAF value in the right parahippocampal gyrus,which was increased FC with the left middle temporal gyrus,inferior temporal gyrus and the left middle occipital gyrus.These discoveries may be the core of the mechanism of impaired brain function in PI patients.

Digestive system tumors account for more than half of all malignant tumors in terms of incidence and mortality,and thus pose a serious threat to human health.Haptoglobin(Hp)is an acute-phase glycoprotein that is elevated in both plasma and tumor tissues in various clinical conditions,including different types of cancer,such as liver,gastric,colorectal,pancreatic,and gallbladder cancer.Numerous studies have indicated that Hp plays a significant role in the prognosis of cancer patients,highlighting its potential as a prognostic marker for gastrointestinal tumors,with important clinical applications.Despite its demonstrated crucial role in the development of various tumors,however,the specific mechanisms of Hp in gastrointestinal tumors remain controversial.This review considers the differential expression and clinical significance of Hp in the five major types of gastrointestinal tumors,to explore its role in different stages of cancer progression and prognosis.This review thus aims to provide reliable and accurate serum biomarkers for the screening,early diagnosis,treatment,and prognosis monitoring of gastrointestinal tumors,with important implications for predicting the survival and prognosis of cancer patients.

Objective To evaluate the protective effects of the traditional Chinese medicine formula Shenxiankang on renal injury and fibrosis,and to explore its potential mechanisms of action.Methods Chronic kidney disease(CKD)model was established in mice using unilateral ureteral obstruction(UUO).The mice were randomly divided into four groups:sham,UUO,and Shenxiankang(SXK)Low/High dose groups(1500,4500 mg/(kg·d)),each comprising eight mice.The each SXK groups received daily oral administration of Shenxiankang,and the remaining mice were gavaged equivalent volumes of saline for 7 d.After the experiment,renal tissues were collected for assessment of renal injury and fibrosis using HE and Masson staining.The expression levels of fibrosis markers and proteins involved in the epithelial membrane protein 3(Emp3)and Tgf-β/Smad3 signaling pathway were determined by Real-time PCR,immunohistochemistry,and Western Blot.In cell-based experiments,the effects of Shenxiankang on the Emp3/Tgf-β/Smad3 pathway and its interaction with TGF-beta receptor R2(Tgfβ2)were further analyzed using an Emp3 knockdown and Co-IP assays.Results Shenxiankang significantly reduced immune cell infiltration and tubular atrophy in the UUO model group and decreased the expression of kidney injury markers kidney injury molecule 1(Kim1)and Lipocalin 2(Lcn2),confirming its efficacy in alleviating renal injury.Masson staining and analysis of fibrosis markers Fibronectin(Fn)and α-smooth muscle actin(α-SMA)indicated that Shenxiankang effectively suppressed fibrosis induced by UUO.Mechanistic studies revealed that Shenxiankang exerted its effects by selectively downregulating the abnormal activation of the Emp3/Tgf-β/Smad3 signaling pathway,a finding further supported by cellular experiments showing that Shenxiankang modulates Tgf-β/Smad3 signaling through Emp3 regulation.Moreover,the Co-IP experiment result indicate that Shenxiankang exerts its effects by regulating the interaction between Emp3 and Tgfβ2.Conclusions Shenxiankang exhibits significant protective effects in a mouse model of chronic kidney disease,effectively reducing renal injury and fibrosis.These effects are likely mediated through the downregulation of the Emp3/Tgf-β/Smad3 signaling pathway,suggesting Shenxiankang's potential therapeutic value in renal protection.

Objective To evaluate the protective effects of the traditional Chinese medicine formula Shenxiankang on renal injury and fibrosis,and to explore its potential mechanisms of action.Methods Chronic kidney disease(CKD)model was established in mice using unilateral ureteral obstruction(UUO).The mice were randomly divided into four groups:sham,UUO,and Shenxiankang(SXK)Low/High dose groups(1500,4500 mg/(kg·d)),each comprising eight mice.The each SXK groups received daily oral administration of Shenxiankang,and the remaining mice were gavaged equivalent volumes of saline for 7 d.After the experiment,renal tissues were collected for assessment of renal injury and fibrosis using HE and Masson staining.The expression levels of fibrosis markers and proteins involved in the epithelial membrane protein 3(Emp3)and Tgf-β/Smad3 signaling pathway were determined by Real-time PCR,immunohistochemistry,and Western Blot.In cell-based experiments,the effects of Shenxiankang on the Emp3/Tgf-β/Smad3 pathway and its interaction with TGF-beta receptor R2(Tgfβ2)were further analyzed using an Emp3 knockdown and Co-IP assays.Results Shenxiankang significantly reduced immune cell infiltration and tubular atrophy in the UUO model group and decreased the expression of kidney injury markers kidney injury molecule 1(Kim1)and Lipocalin 2(Lcn2),confirming its efficacy in alleviating renal injury.Masson staining and analysis of fibrosis markers Fibronectin(Fn)and α-smooth muscle actin(α-SMA)indicated that Shenxiankang effectively suppressed fibrosis induced by UUO.Mechanistic studies revealed that Shenxiankang exerted its effects by selectively downregulating the abnormal activation of the Emp3/Tgf-β/Smad3 signaling pathway,a finding further supported by cellular experiments showing that Shenxiankang modulates Tgf-β/Smad3 signaling through Emp3 regulation.Moreover,the Co-IP experiment result indicate that Shenxiankang exerts its effects by regulating the interaction between Emp3 and Tgfβ2.Conclusions Shenxiankang exhibits significant protective effects in a mouse model of chronic kidney disease,effectively reducing renal injury and fibrosis.These effects are likely mediated through the downregulation of the Emp3/Tgf-β/Smad3 signaling pathway,suggesting Shenxiankang's potential therapeutic value in renal protection.

AIM:To investigate the efficacy of Shenxiankang(SXK)in mitigating renal fibrosis in unilateral ureteral obstruction(UUO)mice,and elucidate its regulatory mechanism targeting the differentiation antagonizing non-protein coding RNA(DANCR)/TGF-β1/Smad3 signaling axis.METHODS:Mice were randomly assigned to:normal group(NC),model group(UUO),low,medium and high doses(1 500,3 000 and 4 500 mg·kg-1·d-1)of SXK group,and benazepril(10 mg·kg-1·d-1)group.Chronic kidney disease was modeled via unilateral ureteral ligation.Renal DAN-CR overexpression was induced using tail vein injection coupled with ultrasound microbubble technology.In vitro,human renal tubular epithelial cells(HK-2)were stimulated with TGF-β1;DANCR was either knocked down or overexpressed,followed by SXK intervention in both in vivo and in vitro models.Renal tissues were harvested for pathological assessment.DANCR expression and localization were analyzed using fluorescence in situ hybridization.Fibrosis deposition was evaluat-ed by immunohistochemistry(IHC).Western blot quantified the expression of fibrosis markers(α-SMA,FN)and key components of the TGF-β1/Smad3 signaling axis(p-Smad3,Smad3,TGF-β1).RESULTS:UUO mice exhibited signifi-cant renal tubular dilation.SXK intervention ameliorated renal lesions and reduced fibrosis.In UUO mice with DANCR overexpression,levels of renal fibrosis markers(α-SMA,FN)and TGF-β1/Smad3 signaling axis proteins(p-Smad3,Smad3,TGF-β1)were increased;these effects were reversed by SXK.In vitro,DANCR knockdown decreased the expres-sion of fibrotic proteins/mRNA and TGF-β1/Smad3 signaling axis components.SXK treatment effectively counteracted the fibrotic injury and TGF-β1/Smad3 signaling axis activation induced by DANCR overexpression.CONCLUSION:SXK ef-fectively mitigates renal fibrosis in UUO mice,potentially through regulation of the DANCR/TGF-β1/Smad3 signaling axis.

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.

Purpose To explore the changes of brain function and network in primary insomnia(PI)patients using the percent amplitude of fluctuation(perAF)combined with functional connectivity(FC).Materials and Methods A total of 51 PI patients and 45 normal controls underwent resting functional magnetic resonance scans in Kunshan Traditional Chinese Medicine Hospital from November 2019 to December 2022,then the perAF value and FC in brain regions of different perAF value between the two groups was analyzed.Pearson correlation analysis was used to investigate the relationships between the altered perAF values and insomnia years,Pittsburgh sleep quality index and Montreal cognitive assessment.Results Compared with healthy group,PI patients had increased perAF values in the left prefrontal lobe(-42 9 45)and decreased perAF values in the right parahippocampal gyrus(27-12-27)[Gaussian random field(GRF)correction,voxel-wise P<0.001,cluster-level P<0.05].FC analysis showed that the right parahippocampal gyrus of PI patients exhibited significantly increased FC with the left middle temporal gyrus,inferior temporal gyrus(-57-15-33)and the left middle occipital gyrus(-30-78 27)(GRF corrected,voxel-wise P<0.001,cluster-level P<0.05).It was noteworthy that the perAF values of the right parahippocampal gyrus were positively correlated with Montreal cognitive assessment of PI patients(r=0.428,P=0.002).Conclusion Specific brain areas in PI patients may exhibit aberrant neuronal activity,mainly manifested as decreased perAF value in the right parahippocampal gyrus,which was increased FC with the left middle temporal gyrus,inferior temporal gyrus and the left middle occipital gyrus.These discoveries may be the core of the mechanism of impaired brain function in PI patients.

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.

Digestive system tumors account for more than half of all malignant tumors in terms of incidence and mortality,and thus pose a serious threat to human health.Haptoglobin(Hp)is an acute-phase glycoprotein that is elevated in both plasma and tumor tissues in various clinical conditions,including different types of cancer,such as liver,gastric,colorectal,pancreatic,and gallbladder cancer.Numerous studies have indicated that Hp plays a significant role in the prognosis of cancer patients,highlighting its potential as a prognostic marker for gastrointestinal tumors,with important clinical applications.Despite its demonstrated crucial role in the development of various tumors,however,the specific mechanisms of Hp in gastrointestinal tumors remain controversial.This review considers the differential expression and clinical significance of Hp in the five major types of gastrointestinal tumors,to explore its role in different stages of cancer progression and prognosis.This review thus aims to provide reliable and accurate serum biomarkers for the screening,early diagnosis,treatment,and prognosis monitoring of gastrointestinal tumors,with important implications for predicting the survival and prognosis of cancer patients.

Colorectal cancer(CRC)is one of the most common malignant life-threatening tumors,with serious impacts on patient quality of life.Src homology 2 domain-containing protein tyrosine phosphatase(SHP2)has recently become a hot topic in the field of cancer research,and has demonstrated a close relationship with CRC.SHP2,encoded by the PTPN11 gene,is a non-receptor tyrosine kinase commonly present in various tissues and cells of the human body.Existing research shows that SHP2 plays a crucial role in regulating CRC and colitis-associated colon cancer(CAC),and the emergence of SHP2 allosteric inhibitors has identified SHP2 as a potential new therapeutic target for patients with CRC.Here we review the structure of SHP2 and its roles in CRC and CAC.