Objective To investigate the effects of Zuogui Jiangtang Tongmai Prescription on short-chain fatty acids(SCFAs)and G protein-coupled receptor 109A(GPR109A)in diabetic atherosclerotic mice;To explore its mechanism of improving diabetic atherosclerosis.Methods ApoE-/-mice were fed with high sugar and high fat diet and intraperitoneal injection of streptozotocin to establish atherosclerosis model of diabetes.After modeling,the mice were randomly divided into the model group,Western medicine group(metformin hydrochloride+atorvastatin),and Zuogui Jiangtang Tongmai Prescription low-,medium-and high-dosage groups(19,38,76 g/kg);and the other C57BL/6J mice were set as the control group,with 6 mice in each group.Each group was given solution for gavage,once a day for 4 weeks.Blood glucose of the mice were detected,HE staining was used to observe the morphology of the aorta,TG,TC,LDL-C and HDL-C contents were detected by fully automated biochemistry analyzers,ELISA was used to detect the contents of serum HbA1c,fasting insulin(FINS),interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α,gas chromatography was used to detect the content of intestinal SCFAs,and RT qPCR and Western blot were used to detect the mRNA and protein expressions of GPR109A in ileal tissue and nuclear factor(NF)-κB p65 in aortic tissue,respectively.Results Compared with the control group,obvious plaques and inflammatory cells infiltration were seen in the aorta of the model group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNF-α contents increased(P<0.01),FINS and HDL-C content decreased(P<0.01),intestinal acetate,propionate,butyric acid,isobutyric acid and isovaleric acid contents decreased(P<0.01),GPR109A mRNA and protein expression in ileal tissue decreased,NF-κB p65 mRNA and protein expression in aortic tissue increased(P<0.01).Compared with the model group,the aortic plaque area and inflammatory cells infiltration were significantly improved in each drug intervention group,the blood glucose and serum HbA1c,TG,TC,LDL-C,IL-1β,IL-6 and TNF-α contents decreased(P<0.05,P<0.01);the FINS and HDL-C content increased(P<0.05,P<0.01),intestinal acetic,propionic,butyric acid,isobutyric acid and isovaleric acid contents increased(P<0.05,P<0.01),GPR109A mRNA and protein expression in ileal tissue increased and NF-κB p65 mRNA and protein expression in ileal tissue decreased decreased(P<0.05,P<0.01).Conclusion Zuogui Jiangtang Tongmai Prescription can improve glucolipid metabolism and inflammatory response in diabetic atherosclerotic mice,which may be related to regulating SCFAs/GPR109A pathway.

Objective To investigate the ameliorative effect and potential mechanism of Cyclocaryae Paliuri Folium in sodium palmitate-induced lipid deposition in HepG2 cells.Methods The effect of sodium palmitate and lyophilized powder of Cyclocaryae Paliuri Folium on the viability of HepG2 cells was determined by the CCK-8 method to determine the subsequent dosage administered.The HepG2 cells were divided into blank group,model group,pioglitazone group and Cyclocaryae Paliuri Folium low-,medium-and high-dosage group,the lipid deposition model of HepG2 cells was established using 350 μmol/L sodium palmitate,the medication group were given pioglitazone and low-,medium-and high-dosage of Cyclocaryae Paliuri Folium(100,250,500 μg/mL)for 12 h respectively.The intracellular lipid deposition was observed by Nile red staining and BODIPY493/503 fluorescent probe staining,the content of TNF-α and IL-6 in supernatant of cell culture medium were detected by ELISA,Western blot was used to detect PI3K,Akt,sterol-regulatory element binding protein-1(SREBP-1),fatty acid synthase(FAS),Bcl-2,Bax protein expression,qPCR was used to detect the mRNA expression of adipose triglyceride lipase(ATGL)and CD36.Results Compared with the blank group,the lipid deposition of HepG2 cells in the model group increased,TNF-α and IL-6 contents in the supernatant of cell culture medium significantly increased(P<0.01),the protein expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax in cells significantly increased,while the protein expression of Bcl-2 significantly decreased(P<0.01),the mRNA expression of ATGL significantly decreased,and the mRNA expression of CD36 significantly increased(P<0.01).Compared with the model group,the intracellular lipid deposition of the pioglitazone group and Cyclocaryae Paliuri Folium groups improved to varying degrees,the contents of TNF-α and IL-6 in the cell supernatant decreased,the expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax proteins decreased,the expression of Bcl-2 protein increased,the expression of ATGL mRNA increased,and the expression of CD36 mRNA decreased,with statistical significance in pioglitazone group and Cyclocaryae Paliuri Folium high-dosage group(P<0.05,P<0.01).Conclusion Cyclocaryae Paliuri Folium may ameliorate sodium palmitate-induced lipid deposition in HepG2 model cells by modulating the PI3K/Akt/SREBP-1/FAS signaling pathway and affecting triacylglycerol metabolism.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective:To investigate the effect and mechanism of Jiedu Xiaoying Patch in rats with Hashimoto's thyroiditis (HT).Methods:Totally 32 rats were randomly divided into a blank group of 8 rats and a model group of 24 rats. The HT rat model was prepared by freely drinking 0.064% sodium iodide solution in the modeling module. 24 successfully modeled rats were randomly divided into model group, selenium yeast group, and patch group, with 8 rats in each group. Starting from the 9th week, the application group applied Jiedu Xiaoying Patch to the surface projection area of the thyroid gland in the neck of rats for 6 hours, once a day, for a total of 6 weeks; the selenium yeast group was orally administered with 21 μg/ml selenium yeast solution at a dose of 0.5 ml/100 g, while the blank group, model group, and patch group were orally administered with equal volumes of physiological saline solution once a day for a total of 6 weeks. The levels of TGAb,TPOAb, Sema 5A, and IL-17A in rat serum were detected by ELISA. The changes of thyroid tissue was observed with HE staining. The relative expression levels of plexin-A1 and plexin-B3 were determined through RT-PCR.Results:Compared with the model group, the levels of TPOAb, TGAb, Sema 5A, and IL-17A decreased ( P<0.05), and the expressions of plexin-A1 and plexin-B3 decreased in the selenium yeast group and the patch group ( P<0.05). The thyroid follicles in the model group were severely damaged, with a large number of lymphocytes infiltrating the interstices; the thyroid follicular structure of the selenium yeast group was relatively intact, and lymphocyte infiltration was reduced compared to the model group. The thyroid follicular structure of the patch group was basically intact, with a small amount of lymphocyte infiltration observed. Conclusion:Jiedu Xiaoying Patch can significantly reduce the levels of TPOAb and TGAb in HT rats. The mechanism may be related to reducing the content of Sema 5A, inhibiting the expressions of receptors plexin-A1 and plexin-B3, reducing the production of inflammatory cytokines such as IL-17A, and inhibiting immune and inflammatory responses.

Objective To compare the efficacy and complications of cupric ion electrochemical therapy and selective suprahemorrhoid resection and stapling surgery for the treatment of grade Ⅲ-Ⅳhemorrhoids.Methods 204 patients with grade Ⅲ-Ⅳ mixed hemorrhoids admitted to our hospital from September 2022 to October 2023 were included as the study subjects.They were divided into two groups using numerical method,with 102 cases in each group.The observation group received copper ion electrochemical therapy,while the control group received selective hemorrhoid mucosal resection and stapling surgery.Compare the surgical outcomes,efficacy,pain scores,anal function scores,quality of life index scores,and incidence of complications between two groups.Results There was no statistically significant difference in gender,age,hemorrhoid grade,surgical time,and hospitalization period between the observation group and the control group(P＞0.05),but the intraoperative blood loss in the observation group was less than that in the control group[(11.37±5.32)ml and(26.72±14.24)ml],and the difference between the two groups was statistically significant(P＜0.05).The severity of pain in the observation group was lower than that in the control group on the 1st and 7th day after surgery(P＜0.05);There was no statistically significant difference in the Wexner anal incontinence scores between the two groups at 1 and 8 weeks after surgery(P＞0.05).The observation group had a better gastrointestinal quality of life index(GIQLI)score than the control group at 2 weeks after surgery[(20.92±4.63)and(26.77±5.03)scores,P＜0.05],and there was no statistically significant difference between the two groups at 8 weeks[(4.38±0.90)and(4.68±1.41)mm,P＞0.05].The total incidence of postoperative complications in both groups was statistically significant(8.8％vs 20.6％,P＜0.05).An average follow-up of six months showed no recurrence.Conclusion Cupric ion electrochemical therapy for mixed hemorrhoids is safe,effective,and has no serious complications,providing a more convenient and minimally invasive treatment method.

Objective:To investigate the role and mechanism of IL-17 in hypertensive heart failure in rats.Methods:The spon-taneously hypertensive(SHR)model of hypertensive heart failure was established by abdominal aortic ligation.IL-17+IgG and IL-17 protein were injected intraperitoneally into the rats with hypertensive heart failure.After 4 weeks,cardiac structure and function were monitored,and peripheral blood and myocardial tissue were collected.The role and mechanism of IL-17 in hypertensive heart failure were studied by HE staining,immunohistochemistry,Western blot,qRT-PCR and ELISA.Results:After intraperitoneal injection of exogenous IL-17,the levels of IL-17,NT-proBNP,P38 and MK2 protein expressions were increased,and the levels of VEGF and Cav1.2 protein expression were decreased.Exogenous intraperitoneal injection of IL-17+IgG blocked IL-17,increased VEGF level and Cav1.2 protein expression,and decreased NT-proBNP level,P38 and MK2 protein expressions.Conclusion:IL-17 can be activated P38 lightning/MK2-Cav1.2 signaling pathways involved in high blood pressure,heart failure and cardiac function in rats damage;inhi-bition of IL-17 can effectively improve the cardiac function damage caused by hypertensive heart failure.

Objective To compare the efficacy and complications of cupric ion electrochemical therapy and selective suprahemorrhoid resection and stapling surgery for the treatment of grade Ⅲ-Ⅳhemorrhoids.Methods 204 patients with grade Ⅲ-Ⅳ mixed hemorrhoids admitted to our hospital from September 2022 to October 2023 were included as the study subjects.They were divided into two groups using numerical method,with 102 cases in each group.The observation group received copper ion electrochemical therapy,while the control group received selective hemorrhoid mucosal resection and stapling surgery.Compare the surgical outcomes,efficacy,pain scores,anal function scores,quality of life index scores,and incidence of complications between two groups.Results There was no statistically significant difference in gender,age,hemorrhoid grade,surgical time,and hospitalization period between the observation group and the control group(P＞0.05),but the intraoperative blood loss in the observation group was less than that in the control group[(11.37±5.32)ml and(26.72±14.24)ml],and the difference between the two groups was statistically significant(P＜0.05).The severity of pain in the observation group was lower than that in the control group on the 1st and 7th day after surgery(P＜0.05);There was no statistically significant difference in the Wexner anal incontinence scores between the two groups at 1 and 8 weeks after surgery(P＞0.05).The observation group had a better gastrointestinal quality of life index(GIQLI)score than the control group at 2 weeks after surgery[(20.92±4.63)and(26.77±5.03)scores,P＜0.05],and there was no statistically significant difference between the two groups at 8 weeks[(4.38±0.90)and(4.68±1.41)mm,P＞0.05].The total incidence of postoperative complications in both groups was statistically significant(8.8％vs 20.6％,P＜0.05).An average follow-up of six months showed no recurrence.Conclusion Cupric ion electrochemical therapy for mixed hemorrhoids is safe,effective,and has no serious complications,providing a more convenient and minimally invasive treatment method.

Objective:To investigate the role and mechanism of IL-17 in hypertensive heart failure in rats.Methods:The spon-taneously hypertensive(SHR)model of hypertensive heart failure was established by abdominal aortic ligation.IL-17+IgG and IL-17 protein were injected intraperitoneally into the rats with hypertensive heart failure.After 4 weeks,cardiac structure and function were monitored,and peripheral blood and myocardial tissue were collected.The role and mechanism of IL-17 in hypertensive heart failure were studied by HE staining,immunohistochemistry,Western blot,qRT-PCR and ELISA.Results:After intraperitoneal injection of exogenous IL-17,the levels of IL-17,NT-proBNP,P38 and MK2 protein expressions were increased,and the levels of VEGF and Cav1.2 protein expression were decreased.Exogenous intraperitoneal injection of IL-17+IgG blocked IL-17,increased VEGF level and Cav1.2 protein expression,and decreased NT-proBNP level,P38 and MK2 protein expressions.Conclusion:IL-17 can be activated P38 lightning/MK2-Cav1.2 signaling pathways involved in high blood pressure,heart failure and cardiac function in rats damage;inhi-bition of IL-17 can effectively improve the cardiac function damage caused by hypertensive heart failure.

Objective To observe the correlation between cortical thickness and pathological deposition of β-amyloid(Aβ)in patients with Alzheimer disease(AD)induced mild cognitive impairment(MCI)or dementia.Methods Totally 22 AD patients were prospectively enrolled and divided into dementia group(n=12)and MCI group(n=10)based on the degree of cognitive impairment,while 17 healthy individuals without cognitive impairment were recruited as control group.MR examination and 18F-florbutaben(18F-FBB)PET imaging were performed,the cortical thickness and Aβ deposition value(Centiloid[CL]value)were calculated and compared among 3 groups and between each 2 groups,then the correlation between the above two indexes was analyzed.Results The cortical thickness in dementia group,MCI group and control group was(2.18±0.14),(2.35±0.08)and(2.36±0.09)mm,respectively,with significant difference among 3 groups(P＜0.05).The cortical thickness in dementia group was significantly thinner than that in MCI group and control group(both P＜0.05).CL value in dementia group,MCI group and control group was 77.97(63.07,95.55),65.51(54.54,90.50)and-1.17(-9.66,4.88),respectively,with significant difference among 3 groups(P＜0.05).CL value in dementia group and MCI group were significantly higher than in control group(both P＜0.05).The cortical thickness was moderately negatively correlated with CL value in MCI group(r=-0.580,P=0.048)but not in the other 2 groups(both P＞0.05).Conclusion The cortical thickness was moderately negatively correlated with abnormal deposition of Aβ in patients with AD induced MCI,but was not during dementia.

Objective To investigate the ameliorative effect and potential mechanism of Cyclocaryae Paliuri Folium in sodium palmitate-induced lipid deposition in HepG2 cells.Methods The effect of sodium palmitate and lyophilized powder of Cyclocaryae Paliuri Folium on the viability of HepG2 cells was determined by the CCK-8 method to determine the subsequent dosage administered.The HepG2 cells were divided into blank group,model group,pioglitazone group and Cyclocaryae Paliuri Folium low-,medium-and high-dosage group,the lipid deposition model of HepG2 cells was established using 350 μmol/L sodium palmitate,the medication group were given pioglitazone and low-,medium-and high-dosage of Cyclocaryae Paliuri Folium(100,250,500 μg/mL)for 12 h respectively.The intracellular lipid deposition was observed by Nile red staining and BODIPY493/503 fluorescent probe staining,the content of TNF-α and IL-6 in supernatant of cell culture medium were detected by ELISA,Western blot was used to detect PI3K,Akt,sterol-regulatory element binding protein-1(SREBP-1),fatty acid synthase(FAS),Bcl-2,Bax protein expression,qPCR was used to detect the mRNA expression of adipose triglyceride lipase(ATGL)and CD36.Results Compared with the blank group,the lipid deposition of HepG2 cells in the model group increased,TNF-α and IL-6 contents in the supernatant of cell culture medium significantly increased(P<0.01),the protein expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax in cells significantly increased,while the protein expression of Bcl-2 significantly decreased(P<0.01),the mRNA expression of ATGL significantly decreased,and the mRNA expression of CD36 significantly increased(P<0.01).Compared with the model group,the intracellular lipid deposition of the pioglitazone group and Cyclocaryae Paliuri Folium groups improved to varying degrees,the contents of TNF-α and IL-6 in the cell supernatant decreased,the expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax proteins decreased,the expression of Bcl-2 protein increased,the expression of ATGL mRNA increased,and the expression of CD36 mRNA decreased,with statistical significance in pioglitazone group and Cyclocaryae Paliuri Folium high-dosage group(P<0.05,P<0.01).Conclusion Cyclocaryae Paliuri Folium may ameliorate sodium palmitate-induced lipid deposition in HepG2 model cells by modulating the PI3K/Akt/SREBP-1/FAS signaling pathway and affecting triacylglycerol metabolism.