ObjectiveTo investigate the effect of astragaloside Ⅳ（AS-Ⅳ） on the proliferation of vascular smooth muscle cells（VSMCs） induced by angiotensin Ⅱ（Ang Ⅱ） based on solute carrier family 7 member 11/glutathione peroxidase 4（SLC7A11/GPX4） pathway. MethodsPrimary rat thoracic aortic VSMCs were cultured by tissue explant method， and the cell types were identified by immunofluorescence. Cell counting kit-8（CCK-8） was used to determine the optimal concentration and time of AS-Ⅳ after Ang Ⅱ stimulation. The experiment was divided into blank group， model group， AS-Ⅳ group（40 μmol·L^-1）， Erastin group（0.5 μmol·L^-1）， Erastin+AS-Ⅳ group（0.5 μmol·L^-1+40 μmol·L^-1）. The blank group was cultured in normal medium， the model group was cultured in medium containing Ang Ⅱ（0.1 μmol·L^-1）， and each administration group was cultured in medium containing Ang Ⅱ（0.1 μmol·L^-1） and the corresponding doses of drug. CCK-8 and plate clone formation assay were used to detect the proliferation of cells in each group， Prussian blue staining was used to detect cell iron deposition， the content of reactive oxygen species（ROS） in cells was detected by fluorescence probe method， the content of malondialdehyde（MDA） was detected by thiobarbituric acid（TBA） method， and the protein levels of SLC7A11 and GPX4 in each group were detected by Western blot. ResultsPrimary rat thoracic aortic VSMCs were successfully cultured by tissue explant method， and immunofluorescence detection showed that positive expression of α-smooth muscle actin（α-SMA） and negative expression of vimentin in the cells， identifying them as VSMCs. The optimal concentration and time of AS-Ⅳ determined by CCK-8 were 40 μmol·L^-1 and 24 h， respectively. Pharmacodynamic studies showed that compared with the blank group， the cell proliferation in the model group increased， the iron deposition in the cells increased， the contents of ROS and MDA increased， and the expression levels of SLC7A11 and GPX4 proteins decreased（P<0.05， P<0.01）. Compared with the model group， the cell proliferation of the AS-Ⅳ group was inhibited， the iron deposition in the cells was decreased， the contents of ROS and MDA were decreased， and the expression levels of SLC7A11 and GPX4 proteins were increased（P<0.05， P<0.01）. While in the Erastin group， the cell proliferation was increased， the iron deposition was increased， ROS and MDA contents were increased， and the expression levels of SLC7A11 and GPX4 proteins were decreased（P<0.05， P<0.01）. Compared with the AS-Ⅳ group， Erastin+AS-Ⅳ group showed increased cell proliferation， increased iron deposition in cells， increased ROS and MDA contents， and decreased expression of SLC7A11 and GPX4 proteins（P<0.05）. Compared with the Erastin group， the cell proliferation in Erastin+AS-Ⅳ group was inhibited， the iron deposition was decreased， the contents of ROS and MDA were decreased， and the expression levels of SLC7A11 and GPX4 proteins were increased（P<0.05， P<0.01）. ConclusionAS-Ⅳ can inhibit ferroptosis by regulating the SLC7A11/GPX4 pathway， so as to weaken the proliferation of VSMCs， thus playing a role in the treatment of atherosclerosis.

BACKGROUND: Chronic kidney disease (CKD) poses a major global health challenge, often foreshadowing poor patient outcomes. The C-reactive protein to albumin ratio (CAR) serves as a pivotal biomarker, demonstrating a strong correlation with adverse outcomes in cardiovascular disease (CVD). This study sought to examine the correlation between CAR and the risk of all-cause and cardiovascular mortality in patients with CKD stages 3-5. METHODS: This study utilized data of CKD patients from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010, with follow-up to December 31, 2019. The optimal CAR cutoff value was identified utilizing the method of maximally selected rank statistics. Multivariable Cox proportional hazards regression model, restricted cubic splines (RCS) model, and subgroup analysis were employed to assess the association between CAR and mortality among CKD patients. RESULTS: During a median (with interquartile range) follow-up period of 115 (112,117) months among 2,841 CKD individuals, 1,893 deaths were observed, including 692 deaths due to CVD events. Based on the RCS analysis, a non-linear correlation was observed between CAR and mortality. Using 0.3 as the optimal CAR cutoff value, the cohort was divided into high and low groups. In the fully adjusted model, CKD patients with high CAR values exhibited an elevated risk of all-cause mortality (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.28-1.83, P < 0.001) and cardiovascular mortality (HR 1.48, 95% CI 1.08-2.02, P = 0.014). Compared to the population aged >65 years (HR 1.32, 95% CI 0.99-1.76, P = 0.064), the risk of cardiovascular mortality was significantly higher in those aged ≤65 years (HR 2.19, 95% CI 1.18-4.09, P = 0.014) with elevated CAR levels. CONCLUSIONS A notable correlation exists between the elevation of CAR and increased all-cause and cardiovascular mortality, suggesting its potential as an independent indicator for evaluating the prognosis of patients with CKD stages 3-5.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Cardiovascular Diseases/blood* ; Male ; Female ; Middle Aged ; C-Reactive Protein/metabolism* ; Aged ; Biomarkers/blood* ; Nutrition Surveys ; Adult ; United States/epidemiology* ; Serum Albumin/analysis*

The spectrum of biopsy-confirmed kidney disease varies with regions and periods. We describe the distribution of pathological types and epidemiological characteristics of kidney diseases in Northwest China due to regional differences in geographical environment, social economy, and dietary habits. Methods: Kidney biopsy cases from 2005 to 2020 in Xijing Hospital were retrospectively analyzed. Pathological characteristics of patients in different periods were analyzed using the t test or chi-square test. Joinpoint regression was used to analyze trends in pathological types and disease spectrum. Results: A total of 10,528 eligible patients were included. Primary glomerular disease (PGD) accounted for the majority of the cases and exhibited an obvious downward trend, whereas secondary glomerular disease (SGD) showed an obvious upward trend. Among PGD, immunoglobulin A nephropathy (IgAN) remained the most common pathological type, and the detection rate of membranous nephropathy (MN) was significantly increased. Among SGD, Henoch-Schönlein purpura nephritis (HSPN) was the most common pathological type and may present a significant characteristic of Northwest China. Diabetic nephropathy (DN) exhibited the most obvious upward trend in the whole process, whereas the fastest growth since 2012 was in hypertensive nephropathy. Conclusion: The proportion of SGD increased whereas PGD declined. IgAN remained the most common PGD, and HSPN was the most common SGD. MN and DN showed the most obvious upward trend among PGD and SGD, respectively. Changes in the spectrum of kidney disease, especially the constituent ratio of SGD, pose a great challenge to public health.

OBJECTIVE To investigate the effect of arctiin （ARC）relieving lipopolysaccharide （LPS）induced inflammatory injury of human nasopharyngeal epithelial cells NP- 69. METHODS The effects of 24 h treatment of 0.000 1，0.001，0.01，0.1， 1.0，10 μmol/L ARC on the proliferation of NP-69 were determined by MTS method. After 0.01，0.1，and 1.0 μmol/L ARC was applied to NP- 69 for 24 h and NP- 69 was pre-treated with 0.01，0.1 and 1.0 μmol/L ARC for 24 h，and then stimulated with 1.0 μg/mL LPS for 24 h，scratch tests were used to detect cell migration in both experiments. LPS stimulated NP- 69 to establish an inflammation injury model. The levels of nitric oxide （NO），tumor necrosis factor α（TNF-α）interleukin-6（IL-6），and IL- 1β in cell supernatants were detected ，and mRNA and protein expression of zonula oecludens protein 1（ZO-1），β-defensin 3（BD3）， Janus kinase 1 （JAK1），signal transducer and activator of transcription 3 （STAT3） in cell supernatant were also detected. RESULTS Compared with normal group ，0.000 1，0.001，0.01，0.1，1.0，10 μmol/L ARC had no effect on the proliferation of NP-69 after 24 h treatment （P＞0.05）. ARC （0.1，1.0 μmol/L）could significantly promote the rate of cell migration （P＜0.05）. For the inflammatory injure of NP- 69 cells stimulated by LPS ，ARC（1.0 μmol/L）could significantly reduce the release of NO ， TNF-α and IL-6（P＜0.05），significantly increased mRNA and protein expression of ZO- 1 and BD 3 but decreased mRNA and protein expression of STAT 3（P＜0.01 or P＜0.05）. CONCLUSIONS ARC has the effect of reducing the inflammatory injury of NP-69 cells induced by LPS ，promoting the physical and immune defense ability of the nasal mucosa epithelial barrierunder inflammatory environment. The mechanism of action may be related to inhibiting IL- 6/JAK1/STAT3 signaling pathway.

Objective: To investigate the effects of insulin-like growth factor 1 receptor (IGF-1R) inhibitor on tubulopathy in diabetic kidney disease (DKD) mice. Methods: C57BL/6J male mice were randomly divided into normal control group (n=10) and DKD model group (n=30), by giving a single intraperitoneal injection of STZ 150 mg/kg to establish a DKD model. After established successfully, the mice in DKD model group were randomly divided into DKD group (n=10), benazepril group (n=10) and IGF-1R inhibitor group (n=10). IGF-1R inhibitor group was given intraperitoneal injection of IGF-1R inhibitor (30 mg·kg^-1·d^-1) and benazepril group was given intraperitoneal injection of benazepril (30 mg·kg^-1·d^-1). Normal control group and DKD group were given an equal amount of normal saline. After 8 weeks of feeding, mice were euthanatized. Body weight and kidney weight were recorded. Blood, urine and kidney samples were collected. Biochemical tests such as blood glucose and urine albumin were measured by automatic biochemical instruments and albumin excretion rate was calculated. Pathological changes of mice were observed by hematoxylin-eosin staining (HE) and periodic acid-schiff staining (PAS). Phosph (p) IGF-1R expression level was determined by immunohistochemistry and Western blotting. Results: Compared with the normal control group, blood glucose, kidney weight/body weight and urinary albumin excretion rate were significantly higher in DKD group (all P<0.01). In DKD mice, glomerular expansion, tubular stenosis, tubular swelling and tubular atrophy were significantly detected. Meanwhile, the number of proximal tubular epithelial (PTE) cells was decreased, and the renal tubular injury scores, the average glomerular volume, and pIGF-1R protein expression were increased (all P<0.05). Compared with the DKD group, albumin excretion rate was significantly reduced (P<0.01), the above pathological changes were alleviated and the effect of IGF-1R inhibitor was more significant. Compared with the DKD group, the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P<0.05). Compared with the benazepril group, the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P<0.05). Conclusion IGF-1R inhibitor has better effect than benazepril on alleviating the tubulopathy of DKD mice.

Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ²=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ²=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ²=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ²=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.

Passive leg raising is widely used in clinic, but it lacks of specialized mechanical raise equipment. It requires medical staff to raise leg by hand or requires a multi-functional bed to raise leg, which takes time and effort. Therefore we have developed a new medical electric leg-raising machine. The equipment has the following characteristics: simple structure, stable performance, easy operation, fast and effective, safe and comfortable. The height range of the lifter is 50-120 cm, the range of the angle of raising leg is 10°-80°, the maximum supporting weight is 40 kg. Because of raising the height of the lower limbs and making precise angle, this equipment can completely replace the traditional manner of lifting leg by hand with multi-functional bed to lift patients' leg and can reduce the physical exhaustion and time consumption of medical staff. It can change the settings at any time to meet the needs of the patient;can be applied to the testing of PLR and dynamically assessing the hemodynamics; can prevent deep vein thrombosis and some related complications of staying in bed; and the machine is easy to be cleaned and disinfected, which can effectively avoid hospital acquired infection and cross infection; and can also be applied to emergency rescue of various disasters and emergencies.

Objective To explore the changes and comparisons of the four biochemical indicator detection for the early renal im‐pairment in multiple myeloma patients .Methods The 54 patients with multiple myeloma of early onset(MM group) and 54 healthy peoples(control group) were retrospectively analyzed .The levels of serum Cystatin C(Cys C) ,creatinine(Cr) ,β2‐microglobulin(β2‐MG) ,and lactate dehydrogenase(LDH) were detected .And the results for statistical analysis .Results The levels of serum Cys C , Cr ,β2‐MG and LDH were higher significantly in the MM group than in the control group ,the difference was statistically significant (P<0 .05) .In the MM group ,the positive rate of Cys C ,Cr ,β2‐MG ,LDH ,combined detection of Cys C and Cr ,combined detection of β2‐MG and LDH ,combined detection of Cys C ,Cr ,β2‐MG and LDH was 63 .0% ,42 .6% ,74 .1% ,61 .1% ,66 .7% ,85 .2% and 96 .3% respectively .The positive rate of Cys C was higher than Cr ,the difference was statistically significant(P<0 .05) .Between the positive rate of combined detection of β2‐MG ,LDH and Cys C ,Cr ,the difference was statistically significant(P<0 .05) .The positive rate of combined detection of the four biochemical tests was the most highest .Conclusion In the early stage of the renal in‐jury in the patients with MM ,the combined detection of the four biochemical tests is most sensitive to discovery the early stage of the renal glomerular function injury .

Objective To evaluate the accuracy of stroke volume variation (SVV) in monitoring the changes in blood volume during laparoscopic surgery.Methods Forty ASA physical status Ⅰ or Ⅱ patients of both sexes,aged 40-64 yr,with body mass index ranged from 20 to 25 kg/m2,scheduled for elective laparoscopic surgery under general anesthesia,were studied.After induction of general anesthesia,baseline registrations of variables were obtained.After establishing pneumoperitoneum,6％ hydroxyethyl starch (HES 130/0.4) 500 ml was infused over 30 min.Before pneumoperitoneum (T1),at 5 min after pneumoperitoneum (T2),immediately before volume expansion (T3) and at 3 min after volume expansion (T4),cardiac output (CO),cardiac index (CI),SV,stroke volume index (SVI) and SVV were monitored and recorded.The changing rate of CI (△CI) was calculated.The criterion for effective volume expansion was △CI ≥ 15％.The ROC curve for SVV in determining the volume expansion responsiveness was plotted,and the diagnostic threshold was determined.The area under the curve and 95％ confidence interval were calculated.Results SVV was significantly lower at T2 than at T1.CO,CI,SV and SVI were significantly higher,and SVV was lower at T4 than at T3.The results of ROC curve analysis showed that a 9.2％ SVV threshold discriminated between responders and non-responders with a sensitivity of 61％ and a specificity of 50％,and the area under the curve (95％ confidence interval) was 0.567 (0.378-0.757).Conclusion SVV is not a suitable index in monitoring the changes in blood volume during laparoscopic surgery.