ObjectiveTo study the mechanism of Shexiang Tongxin Dripping pills-containing serum （STDP） in ameliorating angiotensinⅡ （AngⅡ）-induced cell phenotype transformation， proliferation， migration， and dysfunction of vascular smooth muscle cells. MethodsAn AngⅡ-induced proliferation and migration model of vascular smooth muscle cells was established. The cells were treated with STDP at 5%， 10%， and 20% for 24 h. The immunofluorescence assay was employed to detect the expression of α smooth muscle actin （α-SMA） and matrix metalloproteinase-2 （MMP-2）. The cell-counting kit-8 （CCK-8） assay and 5-ethynyl-2'-deoxyuridine （EdU） staining were employed to detect the proliferation of vascular smooth muscle cells， and the scratch assay was employed to detect the migration of the cells. Western blot was employed to determine the expression levels of pathway proteins such as angiotensin-converting enzyme 2 （ACE2）， angiotensin Ⅱ type 2 （AT2）， angiotensin Ⅱ type 1 （AT1）， as well as proliferation and migration proteins such as typeⅠ collagen （ColⅠ） and osteopontin （OPN）. ResultsCompared with the model group， STDP increased the expression of α-SMA， reduced the expression of MMP-2， and inhibited the proliferation and migration of vascular smooth muscle cells （P<0.05）. Furthermore， STDP up-regulated the expression levels of ACE2， AT2， and MAS1， while down-regulating the expression level of AT1， PCNA， ColⅠ， MMP-9， Rock1， Rock2， and SRF （P<0.05）. Compared with the STDP group， the ACE2 inhibitor reversed the regulatory effects of STDP. ConclusionSTDP inhibits the phenotype transformation， proliferation， and migration of vascular smooth muscle cells and regulates the expression of cell proliferation and migration-related proteins to ameliorate the dysfunction of vascular smooth muscle cells. It exerts the effects by up-regulating the expression of proteins in the ACE2-AT2/MAS pathway and down-regulating the expression of proteins in the AT1-Rock signaling pathway.

Objective: To investigate the effects of Zuogui Jiangtang Yishen Formula (左归降糖益肾方, ZGJTYSF) in regulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) signaling axis on pyroptosis in rats with diabetic kidney disease (DKD). Methods: Fifty male specific pathogen-free (SPF) grade Goto-Kakizaki (GK) rats (12 weeks old) were fed a high-fat diet for one month to establish an early DKD model. Model establishment was confirmed when fasting blood glucose (FBG) ≥ 11.1 mmol/L and urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. The successfully modeled early DKD rats were randomly divided by random number table into five groups (n = 10 per group): model group; dapagliflozin group (1.0 mg/kg, by gavage, served as positive control); and low-, medium-, and high-dose of ZGJTYSF groups (4.9, 9.9, and 19.9 g/kg, respectively, by gavage). Age-matched male SPF Wistar rats (n = 10) served as control group. Rats in control and model groups were gavaged with equivalent volumes of distilled water. Treatment lasted 12 weeks. Changes in uACR, FBG, and renal function were observed in all groups. Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining were used to observe renal histopathological changes. Immunohistochemistry was performed to detect the localization and expression of caspase-1, GSDMD, and NLRP3 in rat renal tissues. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was utilized to detect pyroptosis in renal tissues. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were applied to detect mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, interleukin (IL)-1β, and IL-18. Results: Compared with model group, all doses of ZGJTYSF showed reductions in FBG, with medium- and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12 (P < 0.05). For uACR, all doses of ZGJTYSF groups exhibited a decreasing trend, with high-dose of ZGJTYSF group being significantly lower than low- and medium-dose of ZGJTYSF groups at week 12 (P < 0.05) and showing no significant difference from dapagliflozin group (P > 0.05). No significant differences in renal function parameters (serum creatinine, blood urea nitrogen, and uric acid) were observed among groups (P > 0.05). Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group, with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group. Immunohistochemistry demonstrated significantly reduced expression of caspase-1, GSDMD, and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group (P < 0.05 or P < 0.01), while the differences in low- and medium-dose of ZGJTYSF groups were not statistically significant (P > 0.05). TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups (P < 0.01), indicating a marked reduction in pyroptotic cells. Molecular analysis revealed that compared with model group, both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 in renal tissues (P < 0.01), while low- and medium-dose of ZGJTYSF groups showed downward trends without statistical significance (P > 0.05). Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis, thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.

ObjectiveTo study the mechanism by which Shexiang Tongxin dropping pills （STDP） ameliorate the dysfunction of coronary microvascular endothelial cells in the rat model of heart failure. MethodsThe heart failure model was established by ligation of the left anterior descending coronary artery in rats， which were then allocated into sham， model， STDP， and telmisartan （TLM） groups and treated for 21 days. The heart function was detected by echocardiography， and the levels of myocardial injury markers， nitric oxide （NO）， endothelin-1 （ET1）， and angiotensinⅡ （AngⅡ） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were determined by Western blot. The model of cardiac microvascular endothelial cell injury was established by AngⅡ induction and then treated with the STDP-containing serum （5%， 10%， and 20%） for 24 h. The levels of NO and ET1 were measured by ELISA. Western blot was employed to determine the protein levels of eNOS， iNOS， angiotensin-converting enzyme 2 （ACE2）， and angiotensinⅡ receptor 2 （AT2）. MLN-4760， an ACE2 inhibitor， was used to explore the mechanism underpinning the regulatory effect of STDP on the ACE2-AT2/MAS pathway. ResultsCompared with the sham group， the model group showed decreases in left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.05）， a decline in serum NO level， elevations in serum AngⅡ and ET1 levels， a reduction in p-eNOS/eNOS ratio， and up-regulation in iNOS expression （P<0.05）. Compared with the model group， STDP increased LVEF， LVFS， and cardiac output （P<0.05）， raised the level of NO and lowered the levels of AngⅡ and ET1 in the serum （P<0.05）， increased the p-eNOS/eNOS value， and inhibited iNOS expression （P<0.05）. Compared with the AngⅡ group， STDP increased the NO content and decreased the ET1 content in endothelial cells （P<0.05）， increased the p-eNOS/eNOS ratio， and inhibited the iNOS expression （P<0.05）. The ACE2 inhibitor MLN-4760 reversed the regulatory effects of STDP on p-eNOS， eNOS， and iNOS. ConclusionSTDP improves the cardiac function in the rat model of heart failure， enhances the synthesis and release of NO in cardiac microvascular endothelial cells， reduces AngⅡ and ET1 levels， and regulates the expression of p-eNOS and eNOS， thereby ameliorating the dysfunction of microvascular endothelial cells in heart failure. This mechanism is related to the upregulation of the expression of proteins in the ACE2-AT2/MAS pathway.

Objective To analyze the correlation between inflammation indicators(systemic inflammatory response syndrome and systemic immune-inflammation index)and adverse outcomes in patients with symptomatic stroke during hospitalization.Methods This study was a prospective cohort study including consecutive patients with symptomatic stroke who were hospitalized in Fuwai Hospital from January to September 2023.The past medical history,clinical symptoms and signs of the patients were collected.The neurological damage was evaluated with National Institute of Health Stroke Scale(NIHSS).Laboratory test results were recorded and the SIRI and SII in-dex were calculated.Patients were followed up for 90 days after the stroke,and their neurological outcomes were evaluated using the modified Rankin Scale.A score of 0-1 was classified as good outcome,and a score ≥2 was classified as poor outcome.The correlation between inflammatory response indicators and poor outcomes was as-sessed using multiple Logistic regression.Results A total of 97 patients with in-hospital symptomatic stroke were included with an average age of 61.8±12.7 years.Among them,there were 28 females(28.9％,28/97),9 with a history of prior stroke(9.3％,9/97),15 with atrial fibrillation(15.5％,15/97),16 with heart failure(16.5％,16/97),and 7 with myocardial infarction(7.2％,7/97).Correlation analysis showed that the NIHSS score at the time of stroke onset was significantly correlated with the patient's post-stroke SIRI(r=0.237,P＜0.05)and SII(r=0.234,P＜0.05).After 90 days of follow-up,41 cases(42.3％,41/97)had a poor outcome.Multiple Logistic regression analysis showed that post-stroke SIRI(Or=4.71,95％CI:1.24-17.90)and SII(Or=3.13,95％CI:0.88-11.06)were correlated with poor outcomes within 90 days after the stroke.Analysis using restricted cubic splines showed that as the levels of SIRI and SII increased,the risk of poor out-comes in patients with in-hospital symptomatic stroke increased.Conclusions SIRI is an independent risk factor for poor outcomes in patients with in-hospital symptomatic stroke,and the risk of poor neurological outcomes in-creases with high level of SIRI.

Objective To establish a rat model of perimenopausal dry eye with liver and kidney yin deficiency from the perspective of"measuring evidence by prescription"in Chinese medicine.Methods Thirty SPF-grade female SD rats were divided randomly into sham-operated,model,and Qiju Dihuang soup groups(n=10).Rats in the latter two groups underwent bilateral ovariectomy and were given 0.1％benzalkonium chloride eye drops combined with provocation for 10 weeks to establish a model of perimenopausal dry eye with liver and kidney yin deficiency.After modeling,rats in the Qiju Dihuang soup group were gavaged with Qiju Dihuang soup at a dose of 8.37 g/(kg·d),rats in the sham-operated and model groups were gavaged with saline at a rate of 1 mL/100(g·d)for 21 d.The general condition,retinal screen test scores,tear secretion,time of tear film rupture,and corneal fluorescein staining were observed and recorded in each group.Serum levels of follicle-stimulating hormone(FSH),estradiol(E2),and progesterone(PROG)were measured by enzyme-linked immunosorbent assay.Pathological damage to the cornea and lacrimal glands were detected by hematoxylin/eosin staining.Expression levels of the inflammatory factors interleukin(IL)-1β and tumor necrosis factor(TNF)-a in the cornea were detected by immunohistochemistry.Results Compared with the sham-operated group,rats in the model group showed behavioral signs of slow action and reaction,irritability,body mass loss,and increased anal temperature(P＜0.05),decreased retinal screen test scores(P＜0.05),tear secretion(P＜0.05),and time of tear film rupture(P＜0.05),and pathological damage to the cornea and lacrimal glands.FSH levels increased and E2 and PROG levels decreased(P＜0.05)and expression levels of IL-1 and TNF-α increased in the model group compared with the sham group.All the above indexes were significantly improved in the Qiju Dihuang soup group compared with the model group.Conclusions From the perspective of"measuring evidence by formula"in Chinese medicine,we successfully established a rat model of perimenopausal dry eye with liver-kidney yin deficiency syndrome,which provides a theoretical and experimental basis for future systematic and in-depth research on the mechanism of perimenopausal dry eye with formula and evidence.

Objective To establish a rat model of perimenopausal dry eye with liver and kidney yin deficiency from the perspective of"measuring evidence by prescription"in Chinese medicine.Methods Thirty SPF-grade female SD rats were divided randomly into sham-operated,model,and Qiju Dihuang soup groups(n=10).Rats in the latter two groups underwent bilateral ovariectomy and were given 0.1％benzalkonium chloride eye drops combined with provocation for 10 weeks to establish a model of perimenopausal dry eye with liver and kidney yin deficiency.After modeling,rats in the Qiju Dihuang soup group were gavaged with Qiju Dihuang soup at a dose of 8.37 g/(kg·d),rats in the sham-operated and model groups were gavaged with saline at a rate of 1 mL/100(g·d)for 21 d.The general condition,retinal screen test scores,tear secretion,time of tear film rupture,and corneal fluorescein staining were observed and recorded in each group.Serum levels of follicle-stimulating hormone(FSH),estradiol(E2),and progesterone(PROG)were measured by enzyme-linked immunosorbent assay.Pathological damage to the cornea and lacrimal glands were detected by hematoxylin/eosin staining.Expression levels of the inflammatory factors interleukin(IL)-1β and tumor necrosis factor(TNF)-a in the cornea were detected by immunohistochemistry.Results Compared with the sham-operated group,rats in the model group showed behavioral signs of slow action and reaction,irritability,body mass loss,and increased anal temperature(P＜0.05),decreased retinal screen test scores(P＜0.05),tear secretion(P＜0.05),and time of tear film rupture(P＜0.05),and pathological damage to the cornea and lacrimal glands.FSH levels increased and E2 and PROG levels decreased(P＜0.05)and expression levels of IL-1 and TNF-α increased in the model group compared with the sham group.All the above indexes were significantly improved in the Qiju Dihuang soup group compared with the model group.Conclusions From the perspective of"measuring evidence by formula"in Chinese medicine,we successfully established a rat model of perimenopausal dry eye with liver-kidney yin deficiency syndrome,which provides a theoretical and experimental basis for future systematic and in-depth research on the mechanism of perimenopausal dry eye with formula and evidence.

ObjectiveTo explore the protective effects and potential mechanism of Zuogui Jiangtang Yishen prescription （ZJYP） in Goto-Kakizaki （GK） rats with early-stage diabetic kidney disease （DKD）. MethodFifty 12-week-old male GK rats were included in this study. DKD was induced after one month of high-fat feeding， with fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1 and urinary albumin/creatinine ratio （ACR） ≥ 30 mg·g^-1 used as model criteria. After successful modeling， DKD rats were randomly divided into five groups （n=10 in each group）： the model group， the western medicine group treated with dapagliflozin （1.0 mg·kg^-1·d^-1）， low-， medium-， and high-dose ZJYP groups （4.9， 9.9， 19.9 g·kg^-1·d^-1 by gavage）. Ten Wistar rats served as normal controls， with both the normal and model groups receiving physiological saline in the same volume as the treatment groups by gavage for 8 weeks. The urinary ACR， FBG， body weight， and liver and kidney functions of the rats were observed. Renal tissues were subjected to haematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining and examined under an electron microscope to observe pathological changes. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect miRNA-27a， Wnt， and β-catenin mRNA and protein expression levels in renal tissues. ResultCompared with the results in the normal group， the FBG levels in DKD rats of the model group increased significantly at 0， 2， 4， 6， and 8 weeks of drug intervention （P<0.05）， and urinary ACR increased significantly at 0， 4， 8 weeks （P<0.05）. Renal pathological staining and electron microscopy revealed an increase in mesangial cells and matrix， slight thickening of the basement membrane， and increased interstitial fibrosis and renal tubular atrophy in the model group. The mRNA expression levels of miRNA-27a， Wnt， and β-catenin were significantly higher in the model group than in the normal group （P<0.05）. Renal Wnt and β-catenin protein levels were also significantly higher in the model group （P<0.05）. After drug intervention， the FBG levels in the low-， medium-， and high-dose ZJYP groups showed a dose-dependent decrease compared with those in the model group at 6 and 8 weeks （P<0.05）. The urinary ACR also showed a dose-dependent decrease in the low-， medium-， and high-dose ZJYP groups， but the differences were not statistically significant. There were no significant differences in liver function， renal function， renal index， or routine blood lipid test results among the low-， medium-， and high-dose ZJYP groups. Renal glomerular and tubular lesions were milder in the ZJYP groups and the western medicine group than in the model group， with similar pathological changes observed in the high-dose ZJYP group and the western medicine group. The renal mRNA levels of miRNA-27a， Wnt， and β-catenin were significantly lower in the high-dose ZJYP group （P<0.05）， and renal Wnt and β-catenin protein levels were significantly lower in both the western medicine group and the high-dose ZJYP group compared with the levels in the model group （P<0.05）. The Wnt and β-catenin protein levels were lower in the renal tissues of the low- and medium-dose ZJYP groups compared with the levels in the model group， but the differences were not statistically significant. ConclusionZJYP can effectively improve glucose metabolism and alleviate early damage in DKD rats， thereby delaying the progression of DKD. Its mechanism may be related to the inhibition of the miRNA-27a/Wnt/β-catenin signaling pathway in renal tissues.

It remains unclear whether heart transplantation is still feasible on patients who develop neurological complications before surgery and underwent successful neurological treatment.This article reported the diagnosis and treatment process of a heart failure patient complicating with acute ischemic stroke,who underwent successful heart transplantation after thrombectomy for acute ischemic stroke,aiming to provide clinical evidence and decision-making plan on diagnosis and treatment options for this group of patients with severe neurological complications.

Objective:To evaluate the long-term efficacy of radiotherapy for elderly patients with esophageal squamous cell carcinoma.Methods:Clinical data of 118 elderly patients aged ≥65 years with esophageal squamous cell carcinoma treated with radiotherapy alone or concurrent chemoradiotherapy in Cancer Hospital affiliated to Xinjiang Medical University from January 2013 to January 2016 were retrospectively analyzed. All patients were randomly divided into the radiotherapy alone ( n=57) and concurrent chemoradiotherapy groups ( n=61). The effective rate, survival rate, adverse reactions and causes of death were compared between two groups. Rate and constituent ratio were used to describe the categorical variables, and Pearson Chi-square test was used for univariate analysis. Results:The effective rate (68.4% vs. 86.9%, P=0.016) and incidence of adverse reactions (21.1% vs. 50.9%, P<0.001) between radiotherapy alone and concurrent chemoradiotherapy groups were significantly differed. The 1-year overall survival rate significantly differed between two groups (75.4% vs. 91.8%, P=0.016), while no significant differences were observed in the 3-year overall survival rate (36.8% vs. 42.7%, P=0.088) and 5-year overall survival rate (10.7% vs. 18.0%, P=0.746). The main cause of death in two groups was recurrence combined with distant metastasis. Conclusion:Compared with the radiotherapy alone, concurrent chemoradiotherapy can significantly improve the effective rate and survival rate for elderly patients with esophageal squamous cell carcinoma, whereas it may increase the incidence of adverse reactions.

Objective Explore a non-contact physiological and psychological detection model based on facial video in simulations of weightlessness effects,research new methods for non-contact heart rate and negative mood state detection in long-term simulations of weightlessness effect analysis.Methods Construct a non-contact physiological and psychological data collection system for fusion analysis of visible light and thermal infrared videos.Collect physiological and psychological data of volunteers in the"Earth Star-Ⅱ"90-day head-down bed rest experiment.A non-contact heart rate detection model based on GCN facial multi-region feature fusion and a non-contact negative mood state detection model considering data reliability were constructed,and the effectiveness of the models were validated with finger clip heart rate and POMS-SF scale as labels.Results The experimental results show that the average difference in the Bland-Altman plot of the non-contact heart rate detection model is-1.26 bpm,and 96.3%of value error detection data falls within the 95%confidence interval,indicating a high consistency between the model detected heart rate and the finger clip heart rate.The non-contact negative mood state detection model achieves an accuracy of>0.85 for detecting tension,depression,anger,and fatigue.Features such as heart rate,AU06,eye gaze,and head pose were observed to be important to mood state detection.Conclusion Non-contact physiological and psychological detection methods not only can be utilized for long-term physiological analysis in simulations of weightlessness effects,but also provide a novel technical approach for on-orbit astronauts health assurance during long-term space flight in the future.