Objective To intelligently adjust the driving force of a remote-controlled drug delivery capsule based on the postural information in intestines,so as to achieve the control of speed and dosage of drug delivery and reduce the energy consuming.Methods A six-axis sensor MPU6050 was used,and its Z axis was coincident with the central axis of the drug delivery capsule so as to made the medicine discharge port pointing to the Z direction.The angular velocities and accelerations of X,Y,Z axes were monitored,transformed to quaternion with built-in digital motion processor,and then converted to Euler angle form.The intelligence adjustment of driving force could be achieved by accessing the real-time attitude angle of the capsule.Results The results of experiments showed that the error between the actual and the attitude angle measured by the sensor was less 1°.Conclusions The intelligent adjustment scheme of driving force of a gastrointestinal remote-controlled drug delivery capsule was designed.The real-time attitude angles of the capsule could be obtained with high spped and precision.This study can provide the theoretical and experimental basis for the intelligent adjustment of the driving force.

The aim of this study is to explore the tissue distribution of PEGylated puerarin in acute myocardial ischemia model rats. Healthy male SD rats were randomly divided into two groups (30 each). Both were given PEGylated puerarin at a dose of 488 mg x kg(-1). After 5 min of medication, one group was normal rats, another group with acute myocardial ischemia was established by peritoneal injection of 50 mg x kg(-1) isoprenaline. After administration, the animals were executed at 30, 60, 90, 120, 150 and 180 min, then heart, liver, spleen, lung, kidney were extracted. The content of puerarin in organ tissue was determined by HPLC. The results showed that the AUC of tissue distribution of PEGylated puerarin in normal rats was liver > kidney > heart ≈ spleen > lung > brain. While the AUC of tissue distribution of PEGylated puerarin in acute myocardial ischemia model rats was liver ≈ heart > kidney > lung ≈ spleen > brain. AUC(heart) of PEGylated puerarin in acute myocardial ischemia model rats was 1.7 times than that of the normal rats, and there was significant difference (P < 0.05). Thus, PEGylated puerarin had a good heart-targeting property in early myocardial infarction area, drugs could accumulate in the ischemic myocardium. It provided important information for further study and clinic use of PEGylated puerarin.

Objective:To evaluate the effect of remote ischemic conditioning (RIC) on left ventricular (LV) myocardial perfusion, myocardial viability, LV remodeling, regional and global LV function serially following acute myocardial infarction (AMI) in Chinese mini-pigs.Methods:AMI was established in 12 Chinese mini-pigs (8 males, 4 females; age: 6-8 months) and they were randomly divided into RIC group ( n=6) and non-RIC group ( n=6). RIC was performed in pigs by blood pressure inflation on the lower limbs for 5 min period and 4 cycles immediately after surgery. A series of myocardial perfusion imaging and gated 18F-fluorodeoxyglucose (FDG) myocardial metabolism PET/CT imaging were performed longitudinally at the 1st, 14th, 28th and 56th days after AMI, and parameters including total perfusion defect (TPD), hibernating myocardium (HM), Scar, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), summed motion score (SMS), summed thickening score (STS) and changes of these parameters were obtained. Independent-samples t test and Mann-Whitney U test were used to analyze data. Results:Nine Chinese mini-pigs survived after surgery and were performed imaging. Compared to non-RIC group ( n=4), HM at the 28th ((6.0±2.4)% vs (17.0±4.6)%; t=-4.158), TPD 14th-1st ((-11.8±5.4)% vs 9.0%(4.5%, 15.0%); z=2.449), TPD 28th-1st ((-15.3±3.9)% vs (12.0±3.0)%; t=-10.071), TPD 56th-1st ((-18.0±6.5)% vs 9.0%(4.5%, 12.0%); z=2.449), HM 28th-1st ((-10.5±6.9)% vs (8.3±2.1)%; t=-4.507), HM 56th-1st (-15.0%(-17.5%, -8.5%) vs 2.0%(0%, 7.0%); z=2.449) and LVEDV 14th-1st (-0.5(-2.5, 0) ml vs (13.0±4.4) ml; z=2.470) were reduced in RIC group ( n=5; all P<0.05). Conclusion:RIC can improve myocardial perfusion, delay LV remodeling in the acute stage and salvage hibernating myocardium in the subacute stage and chronic stage.

Objective: To explore the role of ROCK1 in oxidized low-density lipoprotein (ox-LDL) induced podocyte injury and its possible mechanism. Methods: The conditionally immortalized mouse podocyte cells were cultured in vitro and exposed to 20 μg/ml ox-LDL for 24 h. Western blotting was used to analyze the expression level of p-MYPT, nephrin, LC3-Ⅱ, p62, p-ULK1 in groups of control, ox-LDL, ROCK1 siRNA with ox-LDL, wtROCK1 with ox-LDL. Podocytes were incubated with DiI labeled ox-LDL for 4 h and fluorescence microscope was used to analyze lipid distribution. Results: Compared with control group, ox-LDL increased cell cholesterol accumulation, activated ROCK along with decreased nephrin, LC3-Ⅱ(P<0.05), and increased p62, and p-ULK1 expression (P<0.05). Over-expression of ROCK1 significantly decreased the expression of nephrin and LC3-Ⅱ, but up-regulated the levels of p62, p-ULK1 and cell cholesterol accumulation in ox-LDL stimulated podocytes (P<0.05). In contrast, Inhibition of ROCK1 protected podocyte by improved lipophagy. Conclusion ROCK1 mediated disfunction of lipophagy contributes to the ox-LDL induced podocyte injury.

Objective:To construct an individualized nomogram prediction model for predicting the risk of the occurrence of covert hepatic encephalopathy (CHE) in patients with liver cirrhosis.Methods:325 cases of liver cirrhosis admitted from January 2020 to December 2022 were selected as the study subjects. Patients were divided into training ( n=213) and validation ( n=112) sets using a cluster randomization method. The risk factors for CHE occurrence in patients with cirrhosis in the training set were analyzed by univariate and multivariate logistic regression. A prediction model related to the nomogram was established. Results:Independent risk factors for the occurrence of CHE in patients with cirrhosis were a history of hepatic encephalopathy, co-infection, gastrointestinal bleeding, severe ascites, prothrombin time ≥16 seconds, high total bilirubin, and high blood ammonia levels ( P<0.05). Nomogram model validation results: The model had a net benefit for the training and validation sets, with C-indices of 0.830 (95% CI: 0.802-0.858) and 0.807 (95% CI: 0.877-0.837), respectively, within the range of 0-96%. The calibration curves of both sets were evenly close to the ideal curves. The AUCs for the ROC curves in both sets were 0.827 (95% CI: 0.796-0.858) and 0.811 (95% CI: 0.787-0.836), respectively. Conclusion:Patients with cirrhosis have many risk factors for CHE occurrence. The nomogram model constructed based on these risk factors possesses a good predictive value for assessing CHE occurrence in cirrhotic patients.

Objective:To learn about the operation of arsenic reduction and water improvement projects and the present situation of arsenic level in drinking water in drinking water type endemic arsenic poisoning areas in Jinzhong City, Shanxi Province.Methods:From May to August 2023, in accordance with the requirements of the "Investigation Plan for Arsenic Content in Drinking Water of Residents in Arsenic Exposed Areas of Shanxi Province", 29 high arsenic villages in the drinking water type endemic arsenic poisoning historical areas of Pingyao County, Jiexiu City and Qi County in Jinzhong City, Shanxi Province were selected as monitoring villages to investigate the operation of water improvement projects. The drinking water samples of village residents were collected and water arsenic level was measured by hydride atomic fluorescence spectrophotometry. At the same time, monitoring of the operation of water improvement projects and water arsenic level for residents within adjacent local areas were carried out in townships where 29 high arsenic villages located.Results:In 2023, a total of 29 high arsenic villages in 3 counties (cities) of Jinzhong City, Shanxi Province were monitored, all of which had undergone water improvement and all water improvement projects were operating normally. The range of water arsenic level was 0.000 - 0.047 mg/L, with 27 high arsenic villages had water arsenic level < 0.01 mg/L. A total of 81 natural villages within the adjacent local areas of high arsenic villages in Jinzhong City were monitored, all of which had undergone water improvement and the water improvement projects were operating normally. The range of water arsenic level was 0.000 - 0.043 mg/L, and there were 4, 7, and 2 natural villages in Pingyao County, Jiexiu City and Qi County with water arsenic level ranging from 0.01 to 0.05 mg/L.Conclusions:All high arsenic villages in Jinzhong City, Shanxi Province have completed water improvement, and the water improvement projects are operating normally. The water arsenic level in most high arsenic villages meets the national drinking water standard (< 0.01 mg/L).

Objective To evaluate the effect of over-expression of phosphatase and tensin homolog does on chromosome ten (PTEN) in podocytes on kidney under high fat diet (HFD) in vivo and clarify the mechanism how PTEN regulates scavenger receptor A (SR-A) expression exposed to oxidized low density lipoprotein (ox-LDL) in podocytes in vitro.Methods The podocyte-specific PTEN knockin (PPKI) mice were fed with HFD to establish mouse model of lipid-induced renal injury.Mice were divided into four groups:ND+Ctrl group,ND+PPKI group,HFD+Ctrl group and HFD+PPKI group.After 24 weeks of dietary intervention,all mice were tested for clinical and biochemical parameters,including serum creatinine (Scr) as well as urine albumin excretion rate (UAER);renal lipid content was measured by oil red O staining and cholesterol quantitative analysis;the pathological changes of glomeruli were observed by PAS staining and electron microscope.Podocyte injury was induced by ox-LDL in vitro.Western blotting was used to detect the changes of SR-A expression induced by ox-LDL after YAP-siRNA interfering (si-YAP),as well as YAP phosphorylation induced by ox-LDL after interfering by PTEN-siRNA (si-PTEN) and PTEN phosphatase inhibitor (Bpv-PTEN),and overexpressing by recombinant adenovirus (ad-PTEN).Results Compared with ND+Ctrl group,HFD+ Ctrl group significantly aggravated the levels of Scr and UAER,the expression of SR-A in podocytes,renal lipid content,mesangial matrix expansion,effacement of podocyte foot processes,and incrassation of glomerular basement membrane (all P ＜ 0.05).Conversely,compared with HFD+Ctrl group,HFD+ PPKI group obviously alleviated the above lipid-induced renal damage (all P ＜ 0.05).In vitro,the expression of SR-A in podocytes was up-regulated when stimulated with ox-LDL (P ＜ 0.05),and the knockout of YAP significantly down-regulated the expression of SR-A induced by ox-LDL (P ＜ 0.05).Exposed to ox-LDL,the expression of p-YAP increased in podocytes (P ＜ 0.05);over-expression of PTEN inhibited p-YAP up-regulation induced by ox-LDL (P ＜ 0.05),while either knockdown of PTEN or inhibition of PTEN phosphatase activity displayed opposite effect (all P ＜ 0.05).Conclusions Over-expression of PTEN in podocytes protected the kidney against damage from HFD in vivo and PTEN might suppress SR-A mediated lipid uptake via dephosphorylating p-YAP to prevent podocyte injury from ox-LDL.

In the development of oxidative stress-relevant diseases, reactive oxygen species (ROS) removal obstacle or excess production results in the damage of the body tissues and organs. Recent studies have demonstrated that nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) axis played a significant role in anti-oxidative stress. The Nrf2/HO-1 axis counteracts oxidative stress injury by its resistance to inflammation, oxidation, mitochondrial damage and calcium influx, apoptosis, pyroptosis, ferroptosis and autophagy, which provides a theoretical basis for its therapeutic effect on various oxidative stress-relevant diseases in multiple organs (respiratory, cardiovascular, nervous, digestive, urinary and blood systems). Therefore, effective regulation of the Nrf2/HO-1 signal axis can be an important strategy for treatment of oxidative stress-relevant diseases.
Heme Oxygenase-1 ; NF-E2-Related Factor 2 ; Oxidative Stress ; Reactive Oxygen Species ; Signal Transduction

Objective To establish a new model of indocyanine green (ICG) clearance test combined with total bilirubin actual resident rate (TBARR) for predicting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) treated with artificial liver support system (ALSS) therapy. Methods A retrospective analysis was performed for the clinical data of 136 patients with HBV-ACLF who underwent ALSS therapy in Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, from June 2017 to July 2021, and according to the prognosis at 3-month follow-up, they were divided into survival group with 92 patients and death group with 44 patients. Related indicators were measured at the time of the confirmed diagnosis of ACLF, including biochemical parameters, coagulation, indocyanine green retention rate at 15 minutes (ICGR 15 ), and effective hepatic blood flow (EHBF), and related indices were calculated, including Model for End-Stage Liver Disease (MELD) score, MELD difference (ΔMELD), Child-Turcotte-Pugh (CTP) score, total bilirubin clearance rate (TBCR), total bilirubin rebound rate (TBRR), and TBARR. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups; the chi-square test was used for comparison of categorical data between groups. A binary logistic regression analysis was used to establish a combined predictive model for the prognosis of HBV-ACLF after ALSS therapy. The area under the ROC curve (AUC) was used to compare the accuracy of various models in judging the short-term prognosis of patients with HBV-ACLF after ALSS therapy, and the Z test was used for comparison of AUC. Results There were significant differences between the death group and the survival group in MELD score, ΔMELD, CTP score, ICGR 15 , EHBF, TBRR, TBARR, neutrophil count, percentage of neutrophils, lymphocyte count, platelet count, alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin, albumin, prothrombin time, international normalized ratio, prothrombin time activity, prealbumin, fibrinogen, serum sodium, age, and the incidence rate of hepatic encephalopathy (all P < 0.05). The multivariate logistic regression analysis showed that age (odds ratio [ OR ]=1.096, 95% confidence interval [ CI ]: 1.056-1.137, P < 0.001), neutrophil count ( OR =1.214, 95% CI : 1.044-1.411, P =0.012), TBRR ( OR =0.989, 95% CI : 0.982-0.996, P =0.001), TBARR ( OR =1.073, 95% CI : 1.049-1.098, P < 0.001), ΔMELD ( OR =1.480, 95% CI : 1.288-1.701, P < 0.001), CTP score ( OR =2.081, 95% CI : 1.585-2.732, P < 0.001), and ICGR 15 ( OR =1.116, 95% CI : 1.067-1.168, P < 0.001) were independent influencing factors for short-term mortality in patients with HBV-ACLF after ALSS therapy. The binary logistic regression analysis was used to establish four combined predictive models for predicting the prognosis of HBV-ACLF after ALSS therapy, i.e., TBRR-ICGR 15 , TBARR-ICGR 15 , TBARR-ICGR 15 -ΔMELD, and TBARR-ICGR 15 -ΔMELD-age, with an AUC of 0.830, 0.867, 0.900, and 0.917, respectively, and the combined predictive models had a larger AUC than each index alone (age, neutrophil count, TBRR, TBARR, ΔMELD, MELD score, CTP score, and ICGR 15 ), among which the TBARR-ICGR 15 -ΔMELD-age model had the largest AUC. The combined models TBARR-ICGR 15 -ΔMELD and TBARR-ICGR 15 -ΔMELD-age had sensitivities and specificities of > 80%. Conclusion The combined predictive model established by ICGR 15 and TBARR has a good value for in predicting the short-term prognosis of patients with HBV-ACLF after ALSS therapy, and the combined predictive model has a better accuracy than the single model in judging prognosis.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.