Objective:To investigate the clinicopathological features including immunophenotype, molecular characteristics, differential diagnosis and prognosis of SMARCB1-deficient renal medullary carcinoma (RMC) without sickle cell trait.Methods:The clinicopathological data of 12 cases of SMARCB1-deficient RMC without sickle cell trait were collected from 7 domestic institutions during the period of 2015 to 2024. Their clinical characteristics, morphological features and immunohistochemical properties were observed and analyzed. High-throughput DNA-targeted next-generation sequencing was performed, and follow-up data were gathered along with relevant literature review.Results:Among the 12 patients, 5 were female and 7 were male. The patients age ranged from 27 to 84 years with a median age of 58.5 (46.0, 71.0) years. None of them had sickle cell disease or other hemoglobinopathies. Eight cases occurred in the left kidney and 4 cases were located in the right kidney. The average maximum diameter of the tumor was 6.1 (4.0,7.5) cm, with a range of 2.0 to 14.9 cm (the median maximum diameter 5.5 cm). Histologically, the tumors showed poorly differentiated adenocarcinoma, arranged in solid and tubular patterns. Papillary structure was noted in 5 cases, cribriform structure in 3 cases, rhabdoid differentiation in 3 cases, and sarcomatoid differentiation in 2 cases. Inflammatory desmoplastic stromal reaction was observed in 8 cases, among which stromal myxoid degeneration was seen in 6 cases. Tumor necrosis was apparent in 6 cases. The tumor cells had abundant eosinophilic or clear cytoplasm and prominent nucleoli. The nuclear grading was grade 3 or 4 according to the International Society of Urological Pathology (ISUP). Immunohistochemical staining showed that the tumor cells of all 12 cases expressed PAX8 and loss of SMARCB1/INI1 protein expression, and 5 of 10 cases expressed OCT3/4. Seven samples had valid archived paraffin tissues for high-throughput DNA-targeted next-generation sequencing. The results showed that all 7 cases had pathogenic mutations in the SMARCB1 gene. The mutation sites included exon5 c.595A>T (p.K199*), exon2 c.200_207del (p.S67*), exon2 p.G69VfsTer16, exon7 c.986G>T (p.S329I), exon7 c.886A>T (p.K296*), exon6 c.635T>A (p.L212*), exon5 c.577del (p.M193Wfs16), and exon6 c.784del (p.V262Sfs5). Follow-up data were obtained for 6 of 12 patients. Among them, 1 patient had lung and bone metastases, 1 patient had liver and bone metastases and 1 patient had multiple bone metastases at the time of diagnosis; 1 patient had bone metastases 5 months after surgery. One patient died of postoperative complications 10 days after surgery, 4 patients died of tumors (the survival time ranged from 4 to 8 months), and 1 patient had no recurrence or metastasis during the 8-month follow-up after surgery.Conclusions:SMARCB1-deficient RMC without sickle cell trait is a highly aggressive and poorly differentiated renal cell carcinoma. It has similar histomorphology, immunophenotype, molecular characteristics and prognosis to RMC, which further supports that it is a sporadic subtype of RMC related to sickle cell trait.

Objective The effect of total polysaccharides on the absorption of small molecule components in Taohong Siwu Decoction was studied.Methods A rat middle cerebral artery occlusion/reper-fusion(MCAO/R)model was established by using thread occlu-sion method.Intragastric administration of THSWD.THSWD small molecule(THSWDX)and THSWDPX(THSWD polysaccharide plus small molecule)was performed once a day for7days each.Brain,serum,stool and colon were collected after the last dose.TTC staining was used to detect the infarct size,HE staining was used to detect the pathology of colon.16S rRNA high-throughput sequencing was used to detect the changes of intestinal flora in rats.Serum metabolite differences were detected by fully targeted metabolomics.Results In the polysaccharide group,the cerebral infarction size was significantly reduced,the colonic crypt structure was intact,goblet cells were abundant,and the epithelial structure was intact.16S rRNA high-throughput sequencing results showed that compared with the model group,the abundance of Bacteroidetes could be decreased in each administration group,especially in THSWD,and the abundance of Pro-teobacteria,Firmicutes and verrucobacteria could be increased at the same time.The amino acid content in each administration group in-creased while the organic acid content decreased,The abundance of Bacteroidetes in the small molecule group administered alone was still high.and the short-chain fatty acid components such as butyric acid and glutaric acid were missing.and there were differences in trypto-phan metabolism and pyrimidine metabolism pathway.Conclusion Polysaccharides and small molecules have synergistic effects.and their main targets are intestinal flora,which are embodied in the following two aspects:①Polysaccharide can improve the structure of the flora,and promote better drug absorption;②Changes in the intestinal floraffect the changes of metabolites.and different metabolites partic-ipate in body metabolism through different ways to accelerate the recovery of the lesion site.

Objective·To investigate the association of insulin resistance with left ventricular(LV)remodeling after ST-segment elevation myocardial infarction(STEMI)in patients without a history of diabetes mellitus.Methods·This study consecutively enrolled STEMI patients without a history of diabetes mellitus who underwent percutaneous coronary intervention in the Department of Cardiology of Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,from January 2014 to December 2022.The patients were followed up for 6 months.Age,gender,smoking status,blood pressure,body mass index,biochemical indexes(liver function,kidney function,lipid profiles,glycemic levels and peak troponin levels,etc.)and pharmacological treatment were recorded.Homeostasis model assessment of insulin resistance(HOMA-IR)was used to evaluate insulin resistance and mean values of visit-to-visit HOMA-IR were calculated.Patients were divided into 4 groups(low-level group,low-to-medium-level group,medium-to-high-level group,and high-level group)according to the quartiles of mean HOMA-IR levels.Echocardiography was performed at baseline and during follow-up.Then the association between mean values of insulin resistance and post-infarction LV remodeling was analyzed.Results·A total of 219 patients were finally included,with an average age of(62.7±11.9)years,and male patients accounted for 85.4％(187 cases).The average follow-up time was(6.4±1.8)months.During follow-up,the average number of HOMA-IR measurements was(4.32±2.18),and the mean value of visit-to-visit HOMA-IR was 2.41(1.58,3.98),which was higher than normal range.The results showed that post-infarction LV end-diastolic diameter(P=0.027)and LV end-diastolic volume index(P=0.013)generally showed a trend for dilation with increasing mean HOMA-IR levels.Pearson correlation analysis revealed the mean values of visit-to-visit HOMA-IR were positively correlated to changes in LV dimensions(△ LV end-diastolic volume index:r=0.20,P=0.003;△ LV end-diastolic diameter:r=0.21,P=0.002).Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI,even after adjusting for age,gender,traditional risk factors(history of hypertension,body mass index,smoking status,renal function and lipid profiles),pharmacological treatment,baseline LV ejection fraction and peak troponin levels.Compared with patients with the lowest quartile of HOMA-IR,those with the highest HOMA-IR quartile exhibited a 7.727 mL/m2 increase in LV end-diastolic volume index(P＜0.001).Conclusion·This study reveals that insulin resistance is prevalent in STEMI patients without a history of diabetes mellitus.Insulin resistance is an independent predictor of adverse LV remodeling in this population.

Objective The effect of total polysaccharides on the absorption of small molecule components in Taohong Siwu Decoction was studied.Methods A rat middle cerebral artery occlusion/reper-fusion(MCAO/R)model was established by using thread occlu-sion method.Intragastric administration of THSWD.THSWD small molecule(THSWDX)and THSWDPX(THSWD polysaccharide plus small molecule)was performed once a day for7days each.Brain,serum,stool and colon were collected after the last dose.TTC staining was used to detect the infarct size,HE staining was used to detect the pathology of colon.16S rRNA high-throughput sequencing was used to detect the changes of intestinal flora in rats.Serum metabolite differences were detected by fully targeted metabolomics.Results In the polysaccharide group,the cerebral infarction size was significantly reduced,the colonic crypt structure was intact,goblet cells were abundant,and the epithelial structure was intact.16S rRNA high-throughput sequencing results showed that compared with the model group,the abundance of Bacteroidetes could be decreased in each administration group,especially in THSWD,and the abundance of Pro-teobacteria,Firmicutes and verrucobacteria could be increased at the same time.The amino acid content in each administration group in-creased while the organic acid content decreased,The abundance of Bacteroidetes in the small molecule group administered alone was still high.and the short-chain fatty acid components such as butyric acid and glutaric acid were missing.and there were differences in trypto-phan metabolism and pyrimidine metabolism pathway.Conclusion Polysaccharides and small molecules have synergistic effects.and their main targets are intestinal flora,which are embodied in the following two aspects:①Polysaccharide can improve the structure of the flora,and promote better drug absorption;②Changes in the intestinal floraffect the changes of metabolites.and different metabolites partic-ipate in body metabolism through different ways to accelerate the recovery of the lesion site.

Objective:To explore the relationship between the morphology of the carotid siphon, its related risk factors, and cerebral blood flow perfusion in patients with arteriosclerotic cerebral small vessel disease (aCSVD), and provide imaging evidence for the etiology of aCSVD.Methods:A total of 130 aCSVD patients hospitalized in the Department of Neurology of the First People′s Hospital of Hefei from March 2022 to June 2024, all of whom underwent multimodal imaging assessments, were enrolled. The baseline data were collected, and the morphology of the carotid siphon was visually evaluated using post-processing of head and neck computed tomography angiography (CTA), which was categorized into U-type ( n=63), C-type ( n=32), and V-type ( n=35). Calcification degree was semi-quantitatively assessed based on transverse CTA images. Cerebral perfusion was measured using magnetic resonance arterial spin labeling. The relationship between different siphon segment morphologies, calcification degrees, their risk factors, and cerebral blood flow perfusion was analyzed using analysis of variance and multinomial Logistic regression. Results:Univariate analysis of the 3 siphon types showed significant differences in low-density lipoprotein cholesterol [U-type (2.44±0.84) mmol/L,V-type (2.21±0.57) mmol/L, C-type (2.89±1.07) mmol/L, F=5.578, P=0.005], calcification degree [Among the 63 cases in the U-type group, 19 cases (30.15%) had mild calcification, 20 cases (31.75%) had moderate calcification, and 24 cases (38.10%) had severe calcification; among the 35 cases in the V-type group, 20 cases (57.14%) had mild calcification, 10 cases (28.57%) had moderate calcification, and 5 cases (14.29%) had severe calcification; among the 32 cases in the C-type group, 12 cases (37.50%) had mild calcification, 14 cases (43.75%) had moderate calcification, and 6 cases (18.75%) had severe calcification; χ2=13.092, P=0.011], and total aCSVD load [modified aCSVD load score: U-type 4.00(1.00, 4.00),V-type 3.00(1.00, 4.00),C-type 2.00(2.00, 4.00), H=9.997, P=0.007]. Multivariate Logistic regression revealed that patients with U-shaped siphons had a significantly higher overall aCSVD load than those with C-shaped siphons, with a regression coefficient of 0.728, and a statistically significant difference ( OR=2.070 ,95% CI 1.026-4.178, P=0.042). Additionally, total brain and white matter cerebral blood flow were decreased in patients with U-type siphons compared to those with C-type and V-type, primarily involving bilateral superior frontal gyri, left orbital frontal gyrus, and left straight gyrus regions (false discovery rate correction, P<0.05). Conclusions:The imaging manifestations of aCSVD are closely related to the shape of the internal carotid artery siphon.The U type siphon is more likely to lead to hemodynamic changes, resulting in decreased global and regional cerebral blood flow, and demonstrating a higher overall burden of aCSVD, which has certain clinical reference value for assessing the etiology of aCSVD.

Objective·To investigate the association of insulin resistance with left ventricular(LV)remodeling after ST-segment elevation myocardial infarction(STEMI)in patients without a history of diabetes mellitus.Methods·This study consecutively enrolled STEMI patients without a history of diabetes mellitus who underwent percutaneous coronary intervention in the Department of Cardiology of Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,from January 2014 to December 2022.The patients were followed up for 6 months.Age,gender,smoking status,blood pressure,body mass index,biochemical indexes(liver function,kidney function,lipid profiles,glycemic levels and peak troponin levels,etc.)and pharmacological treatment were recorded.Homeostasis model assessment of insulin resistance(HOMA-IR)was used to evaluate insulin resistance and mean values of visit-to-visit HOMA-IR were calculated.Patients were divided into 4 groups(low-level group,low-to-medium-level group,medium-to-high-level group,and high-level group)according to the quartiles of mean HOMA-IR levels.Echocardiography was performed at baseline and during follow-up.Then the association between mean values of insulin resistance and post-infarction LV remodeling was analyzed.Results·A total of 219 patients were finally included,with an average age of(62.7±11.9)years,and male patients accounted for 85.4％(187 cases).The average follow-up time was(6.4±1.8)months.During follow-up,the average number of HOMA-IR measurements was(4.32±2.18),and the mean value of visit-to-visit HOMA-IR was 2.41(1.58,3.98),which was higher than normal range.The results showed that post-infarction LV end-diastolic diameter(P=0.027)and LV end-diastolic volume index(P=0.013)generally showed a trend for dilation with increasing mean HOMA-IR levels.Pearson correlation analysis revealed the mean values of visit-to-visit HOMA-IR were positively correlated to changes in LV dimensions(△ LV end-diastolic volume index:r=0.20,P=0.003;△ LV end-diastolic diameter:r=0.21,P=0.002).Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI,even after adjusting for age,gender,traditional risk factors(history of hypertension,body mass index,smoking status,renal function and lipid profiles),pharmacological treatment,baseline LV ejection fraction and peak troponin levels.Compared with patients with the lowest quartile of HOMA-IR,those with the highest HOMA-IR quartile exhibited a 7.727 mL/m2 increase in LV end-diastolic volume index(P＜0.001).Conclusion·This study reveals that insulin resistance is prevalent in STEMI patients without a history of diabetes mellitus.Insulin resistance is an independent predictor of adverse LV remodeling in this population.

Objective:To investigate the clinicopathological features including immunophenotype, molecular characteristics, differential diagnosis and prognosis of SMARCB1-deficient renal medullary carcinoma (RMC) without sickle cell trait.Methods:The clinicopathological data of 12 cases of SMARCB1-deficient RMC without sickle cell trait were collected from 7 domestic institutions during the period of 2015 to 2024. Their clinical characteristics, morphological features and immunohistochemical properties were observed and analyzed. High-throughput DNA-targeted next-generation sequencing was performed, and follow-up data were gathered along with relevant literature review.Results:Among the 12 patients, 5 were female and 7 were male. The patients age ranged from 27 to 84 years with a median age of 58.5 (46.0, 71.0) years. None of them had sickle cell disease or other hemoglobinopathies. Eight cases occurred in the left kidney and 4 cases were located in the right kidney. The average maximum diameter of the tumor was 6.1 (4.0,7.5) cm, with a range of 2.0 to 14.9 cm (the median maximum diameter 5.5 cm). Histologically, the tumors showed poorly differentiated adenocarcinoma, arranged in solid and tubular patterns. Papillary structure was noted in 5 cases, cribriform structure in 3 cases, rhabdoid differentiation in 3 cases, and sarcomatoid differentiation in 2 cases. Inflammatory desmoplastic stromal reaction was observed in 8 cases, among which stromal myxoid degeneration was seen in 6 cases. Tumor necrosis was apparent in 6 cases. The tumor cells had abundant eosinophilic or clear cytoplasm and prominent nucleoli. The nuclear grading was grade 3 or 4 according to the International Society of Urological Pathology (ISUP). Immunohistochemical staining showed that the tumor cells of all 12 cases expressed PAX8 and loss of SMARCB1/INI1 protein expression, and 5 of 10 cases expressed OCT3/4. Seven samples had valid archived paraffin tissues for high-throughput DNA-targeted next-generation sequencing. The results showed that all 7 cases had pathogenic mutations in the SMARCB1 gene. The mutation sites included exon5 c.595A>T (p.K199*), exon2 c.200_207del (p.S67*), exon2 p.G69VfsTer16, exon7 c.986G>T (p.S329I), exon7 c.886A>T (p.K296*), exon6 c.635T>A (p.L212*), exon5 c.577del (p.M193Wfs16), and exon6 c.784del (p.V262Sfs5). Follow-up data were obtained for 6 of 12 patients. Among them, 1 patient had lung and bone metastases, 1 patient had liver and bone metastases and 1 patient had multiple bone metastases at the time of diagnosis; 1 patient had bone metastases 5 months after surgery. One patient died of postoperative complications 10 days after surgery, 4 patients died of tumors (the survival time ranged from 4 to 8 months), and 1 patient had no recurrence or metastasis during the 8-month follow-up after surgery.Conclusions:SMARCB1-deficient RMC without sickle cell trait is a highly aggressive and poorly differentiated renal cell carcinoma. It has similar histomorphology, immunophenotype, molecular characteristics and prognosis to RMC, which further supports that it is a sporadic subtype of RMC related to sickle cell trait.

Objective:To investigate the effects of miR-7-5p on the proliferation,apoptosis,and immune escape of esophageal squamous cell carcinoma(ESCC)KYSE-150 cells by regulating forkhead box M1(FOXM1).Methods:The targeted binding sites of miR-7-5p and FOXM1 were verified by the dual-luciferase reporter gene assay.The cancer tissues and adjacent paracancerous tissues as well as the basic clinical data of 56 ESCC patients hospitalized at Changzhou Geriatric Disease Hospital affiliated to Soochow University between January 2022 and October 2024 were collected.qRT-PCR was used to detect the expression levels of miR-7-5p and FOXM1 in ESCC tissues,and analyze the relationship between their expressions and clinicopathological characteristics.Normal cultured KYSE-150 cells were selected as the Control group Plasmids were transfected into KYSE-150 cells using Lipofectamine 3000 transfection reagent,and the cells were assigned into the Mimic-NC group,the miR-7-5p mimic group,the miR-7-5p mimic+OE-NC group,and the miR-7-5p mimic+OE-FOXM1 group.EdU staining and CCK-8 assay were used to detect the proliferation ability of KYSE-150 cells.Flow cytometry was performed to detect the apoptosis of KYSE-150 cells and CD8+T cells.Western blot assay was performed to detect the expression levels of PD-L1,FOXM1,BAX,and PCNA proteins in KYSE-150 cells.A nude mouse transplanted tumor model of KYSE-150 cells was established to observe the effects of miR-7-5p overexpression on the growth of the transplanted tumors and the expressions of Ki-67 and FOXM1 in the tissues.Results:miR-7-5p could target and negatively regulate FOXM1(P<0.05).miR-7-5p expression was low and FOXM1 expression was high in ESCC tissues(both P<0.05).The expressions of miR-7-5p and FOXM1 were significantly correlated with TNM stage and differentiation degree,respectively(all P<0.05).The rates of EdU-positive cells,cell proliferation ability,CD8+T cell apoptosis rate,as well as PD-L1,PCNA,and FOXM1 mRNA and protein in the miR-7-5p overexpression group were significantly reduced(all P<0.05),while the apoptosis rate,miR-7-5p,and BAX increased significantly(all P<0.05).Meanwhile,overexpression of FOXM1 could reverse the above effects(all P<0.05).Overexpression of miR-7-5p decreased the mass and volume of transplanted tumors,and the expressions of Ki-67 and FOXM1 proteins in transplanted tumor tissues(all P<0.05).Conclusion:Overexpression of miR-7-5p can significantly inhibit the proliferation and immune escape of KYSE-150 cells and promote cell apoptosis,which may be achieved by targeted negative regulation of FOXM1.

Objective:To explore the relationship between the morphology of the carotid siphon, its related risk factors, and cerebral blood flow perfusion in patients with arteriosclerotic cerebral small vessel disease (aCSVD), and provide imaging evidence for the etiology of aCSVD.Methods:A total of 130 aCSVD patients hospitalized in the Department of Neurology of the First People′s Hospital of Hefei from March 2022 to June 2024, all of whom underwent multimodal imaging assessments, were enrolled. The baseline data were collected, and the morphology of the carotid siphon was visually evaluated using post-processing of head and neck computed tomography angiography (CTA), which was categorized into U-type ( n=63), C-type ( n=32), and V-type ( n=35). Calcification degree was semi-quantitatively assessed based on transverse CTA images. Cerebral perfusion was measured using magnetic resonance arterial spin labeling. The relationship between different siphon segment morphologies, calcification degrees, their risk factors, and cerebral blood flow perfusion was analyzed using analysis of variance and multinomial Logistic regression. Results:Univariate analysis of the 3 siphon types showed significant differences in low-density lipoprotein cholesterol [U-type (2.44±0.84) mmol/L,V-type (2.21±0.57) mmol/L, C-type (2.89±1.07) mmol/L, F=5.578, P=0.005], calcification degree [Among the 63 cases in the U-type group, 19 cases (30.15%) had mild calcification, 20 cases (31.75%) had moderate calcification, and 24 cases (38.10%) had severe calcification; among the 35 cases in the V-type group, 20 cases (57.14%) had mild calcification, 10 cases (28.57%) had moderate calcification, and 5 cases (14.29%) had severe calcification; among the 32 cases in the C-type group, 12 cases (37.50%) had mild calcification, 14 cases (43.75%) had moderate calcification, and 6 cases (18.75%) had severe calcification; χ2=13.092, P=0.011], and total aCSVD load [modified aCSVD load score: U-type 4.00(1.00, 4.00),V-type 3.00(1.00, 4.00),C-type 2.00(2.00, 4.00), H=9.997, P=0.007]. Multivariate Logistic regression revealed that patients with U-shaped siphons had a significantly higher overall aCSVD load than those with C-shaped siphons, with a regression coefficient of 0.728, and a statistically significant difference ( OR=2.070 ,95% CI 1.026-4.178, P=0.042). Additionally, total brain and white matter cerebral blood flow were decreased in patients with U-type siphons compared to those with C-type and V-type, primarily involving bilateral superior frontal gyri, left orbital frontal gyrus, and left straight gyrus regions (false discovery rate correction, P<0.05). Conclusions:The imaging manifestations of aCSVD are closely related to the shape of the internal carotid artery siphon.The U type siphon is more likely to lead to hemodynamic changes, resulting in decreased global and regional cerebral blood flow, and demonstrating a higher overall burden of aCSVD, which has certain clinical reference value for assessing the etiology of aCSVD.

Objective To investigate the correlation between the appendicular skeletal mass index(ASMI)and os-teoporosis(OP)in postmenopausal patients with type 2 diabetes(T2DM).Methods 164 hospitalized postmeno-pausal elderly T2DM patients were selected and their bone density(BMD)and appendicular skeletal mass were measured using dual energy X-ray absorption method(DXA).ASMI=appendicular skeletal mass/height2(kg/m2),and they were divided into OP group and non OP group based on T value.The general clinical data,blood biochemical indicators,and ASMI between the two groups were compared,and Logistic regression analysis,ROC curve were further used to analyze the correlation and diagnostic power.Results Compared with non OP group,OP group had a higher incidence of sarcopenia(SAC)(P＜0.05);the differences in age,ASMI,body mass index(BMI),and estradiol(E2)had significant differences between the two groups(P＜0.05);Logistic regression analysis showed that the reduction of ASMI[OR=0.133,95％CI(0.029-0.611)],BMI[OR=0.785,95％CI(0.625-0.985)],and E2[OR=0.967,95％CI(0.942-0.993)]were protective factors for OP;receiver operating curve(ROC)suggested that the AUC of ASMI for OP prediction was 0.752[95％CI(0.632-0.872),P＜0.001]with sensitivity 87.5％,specificity 47.8％,and the best diagnostic value was 5.52 kg/m2.Conclusion The reduction of ASMI,BMI,and E2 is positively correlated with the occurrence of osteoporosis.ASMI is an important protective factor for osteoporosis.Early OP screening and risk factor assessment should be conducted for elderly postmenopausal T2DM patients,and early intervention measures should be taken to reduce the risk of falls and fractures.