Objective: To establish a method for simultaneous determination of calceolarioside B and chlorogenic acid in Caulis Stauntoniae Chinensis tablets by HPLC.
Methods: The analysis was performed on a Thermo BDS HYPERSIL C₁₈ column (4.6 mm×250 mm,5 μm) maintained at 35 ℃. The mobile phase was consisted of methanol and 0.1% phosphoric acid solution, and gradient eluted with a flow rate of 1.0 mL·min^-1. The detection wavelength was 327 nm, and the injection volume was 10 μL.
Results: The linear ranges of calceolarioside B and chlorogenic acid were 0.51-20.60 μg·mL^-1 (r=1.000) and 0.52-20.63 μg·mL^-1 (r=1.000), respectively. The average recoveries were 100.3% with RSD as 1.1% and 105.9% with RSD as 1.4%, respectively. The content results of 5 batches of Caulis Stauntoniae Chinensis tablets were 0.083-1.115 mg·g^-1 for calceolarioside B and 0.161-1.204 mg·g^-1 for chlorogenic acid.
Conclusion: The method can be used for improving the quality evaluation standard of Caulis Stauntoniae Chinensis tablets.

Objective To investigate the effect of NaAsO2 on ferroptosis in human hepatic stellate cells(LX-2).Methods LX-2 cells were cultured in vitro,and different concentrations of NaAsO2(5μmol/L,10μmol/L,15μmol/L)were infected with LX-2 cells for 24h in a group design to construct the activation model of LX-2 induced by NaAsO2 in vitro,and a control group was set up.Mitochon-drial structure of LX-2 cells treated with NaAsO2 was observed by transmission electron microscopy(TEM).Fe2+levels were detected by fluorescence microscope and fluorescent enzyme label.The content of malondialdehyde(MDA)was determined by the colorimetric meth-od.The protein expression levels of SLC7A11,GPX4,and α-smooth muscle actin(α-SMA)were detected by Western blot.Results TEM showed that mitochondrial membrane integrity was damaged and mitochondrial ridges were reduced and disappeared in the NaAsO2group.In addition,compared with the control group,Fe2+levels in NaAsO2 treatment groups were increased(P＜0.05).There were statistically significant differences in MDA content among different doses of NaAsO2groups(F=7.18,P＜0.05).Compared with the control group,MDA content of LX-2 cells in 5 and 15μmol/L NaAsO2groups was higher than that in the control group(P＜0.05).At the translation level,the expression of fibrosis index α-SMA protein level was up-regulated with the increase of NaAsO2dose(P＜0.05),the protein expression levels of ferroptosis index SLC7A11 and GPX4decreased in a dose-dependent manner with the increase of the dose of NaAsO2(P＜0.05).Conclusion Ferroptosis is involved in the activation of LX-2 cells induced by NaAsO2.

Objective:To study the effect of insulin intraperitoneal administration combined with dietary intervention on glycemic regulation in in KKAy mice with spontaneous type 2 diabetes.Methods:An animal model of type 2 diabetes was established, and healthy C57BL/6J mice were selected as the normal control group and healthy KKAy mice as the non-disease group. The successfully modeled KKAy mice were randomly divided into the subcutaneous group, the intraperitoneal group, and the untreated group. The non-disease group was given a maintenance diet, and all other groups were fed a high-fat, high-sugar diet. The daily feeding time was from 08:00 to 20:00, with one feeding at a 4-hour interval, for a total of four times. The subcutaneous and intraperitoneal groups were given subcutaneous and intraperitoneal insulin injections before feeding, and recombinant glargine insulin injection (subcutaneous group: 0.125 IU/g; intraperitoneal group: 0.250 IU/g) was injected before the first feeding, and biosynthetic human insulin injection (subcutaneous group: 0.075 IU/g; intraperitoneal group: 0.125 IU/g) was injected after a 0.5 h interval; the rest 3 times before feeding, the biosynthetic human insulin injection (subcutaneous group: 0.075 IU/g; intraperitoneal group: 0.125 IU/g) was injected for 4 weeks. The dietary intake, body mass, fasting blood glucose, and 1 and 2 h postprandial blood glucose of mice in each group were tested regularly, and an oral glucose tolerance test was performed.Results:The total dietary intake of mice in the intraperitoneal group was lower than that in the subcutaneous group. Compared with the initial body mass, the body mass of the mice in the subcutaneous and intraperitoneal groups decreased by 5.05 and 3.59 g at week 4, respectively. The changes of fasting blood glucose in the subcutaneous and intraperitoneal groups ranged from 5.4 to 9.4 and 5.4 to 6.4 mmol/L, respectively, and the changes of 1 h postprandial blood glucose ranged from 4.6 to 12.3 and 5.7 to 8.9 mmol/L, respectively, and the changes of 2 h postprandial blood glucose ranged from 2.5 to 9.8 and 3.8 to 7.1 mmol/L, respectively. For the glucose tolerance index, the intraperitoneal group showed improvement at all time points, and the subcutaneous group showed a decrease at all time points except for 0 and 60 min.Conclusions:In combination with dietary intervention, insulin intraperitoneal injection was more effective in controlling blood glucose in KKAy mice with spontaneous type 2 diabetes compared with subcutaneous insulin injection, and had a significant improvement in glucose tolerance.

Objective:To analyze DNA methylation sites related to fibrosis and autophagy in human hepatic stellate cells (LX-2 cells) induced by sodium arsenite (NaAsO 2), and to screen specific methylation genes related to fibrosis and autophagy. Methods:Genome-wide DNA detection was performed using Illumina Infinium Methylation EPIC BeadChips (850K methylation chip) to derive differential methylation sites in LX-2 cells (control group) and the fibrosis and autophagy models of LX-2 cells induced by NaAsO 2(low, medium and high dose groups: the final concentrations were 5, 10, 15 μmol/L NaAsO 2, respectively, after 48 h intervention). Gene ontology (GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis were used to explore gene function. Results:The model of cell fibrosis and autophagy was established successfully in high dose group. The results of 850K methylation chip detection showed that there were 25 817 significant different methylation sites between the high dose group and the control group, including 12 083 hypermethylation sites and 13 734 hypomethylation sites. GO function enrichment analysis showed that the molecular functions of differentially methylated genes mainly included protein binding, ion binding, catalytic activity, enzyme binding. KEGG signaling pathway enrichment analysis showed that the pathways involved in differentially methylated genes mainly included metabolic pathway, cancer pathway, phosphatidylinositol-3-kinase-protein kinase B (PI3K-Akt) signaling pathway, endocytosis, and mitogen activated protein kinase (MAPK) signaling pathway. In the promoter region, 11 and 29 differentially methylated genes related to fibrosis and autophagy were screened, respectively.Conclusions:A large number of differential methylation sites exist in the process of NaAsO 2 induced fibrosis and autophagy of LX-2 cells. Specific methylation genes related to fibrosis and autophagy are screened out.

Inorganic arsenic (iAs) is a common carcinogen that exists in the environment. Liver, as the main target organ of arsenic metabolism, long-term exposure to iAs can ultimately lead to carcinogenesis through two stages: liver fibrosis and cirrhosis. Ferroptosis is a type of programmed cell death caused by the accumulation of iron dependent lipid peroxides that affects the normal function of mitochondria. It has been found that ferroptosis occurs during liver fibrosis. Liver fibrosis caused by iAs has been a global health problem for a long time, but so far there is no effective treatment. The discovery of ferroptosis provides a new way to solve this problem. Therefore, this article will review the research progress of the mechanism of liver injury caused by iAs and ferroptosis.

Objective To evaluate the effect of preoperative pulmonary artery pressure on perioperative prognosis of the recipients with end-stage heart failure undergoing heart transplantation. Methods Clinical data of 105 recipients receiving heart transplantation were retrospectively analyzed. The mean pulmonary artery pressure (mPAP) was used as the diagnostic criterion. The optimal cut-off value of mPAP for predicting perioperative prognosis of heart transplant recipients was determined. According to the optimal cut-off value of mPAP, all recipients were divided into the low mPAP group (n=66) and high mPAP group (n=39). Intraoperative indexes (cardiopulmonary bypass time, aortic occlusion time, assisted circulation time and cold ischemia time of donor heart) and postoperative indexes [intra-aortic balloon pump (IABP) support rate, IABP support time, extracorporeal membrane oxygenation (ECMO) support rate, ECMO support time, mechanical ventilation time, length of ICU stay, incidence of moderate and severe tricuspid regurgitation and perioperative mortality rate] were compared between the low and high mPAP groups. The prognosis of the two groups was compared. Results The optimal cut-off value of mPAP in predicting clinical prognosis of heart transplant recipients was 30.5 mmHg. In the high mPAP group, the ECMO support rate and perioperative mortality rate were higher than those in the low mPAP group (both P < 0.05). No significant differences were observed in the cardiopulmonary bypass time, aortic occlusion time, assisted circulation time, cold ischemia time of donor heart, IABP support rate, IABP support time, ECMO support time, mechanical ventilation time, length of ICU stay and incidence of moderate and severe tricuspid regurgitation between two groups (all P > 0.05). No significant differences were noted in the 1-, 2-, 3- and 4- survival rates between two groups (all P > 0.05). Conclusions Preoperative mPAP in patients with end-stage heart failure is intimately correlated with perioperative prognosis of heart transplant recipients. The optimal cut-off value of mPAP in predicting perioperative prognosis of heart transplant recipients is 30.5 mmHg. In the high mPAP group, perioperative ECMO support rate and perioperative mortality rate are high, which do not affect the medium and long-term prognosis of the recipients undergoing heart transplantation.

Objective: To examine the effect of chronic exposure to sodium arsenite on liver damages in rats. Methods: Fifty-six healthy adult SD rats (28 males and 28 females) were randomly divided into 4 groups. Rats in the low-, medium- and high-dose groups were given sodium arsenite solutions at doses of 2, 10 and 50 mg/L for successive 24 weeks, while animals in the control group were given deionized water. The rat body and liver weights were measured and the liver coefficient was estimated. The urine arsenic level was detected using atomic fluorescence spectrometry, and hepatic tissue sections were stained with uranium acetate and lead citrate for morphological observations under an electron microscope. Results: The body weights of both male and female rats appeared a tendency towards a rise with the duration of exposure to sodium arsenite (male rat: Wald χ2=3 610.621, P<0.001; female rat: Wald χ2=2 186.217, P<0.001, and there were no significant differences in the rat body weight 24 weeks post-exposure to sodium arsenite in each group, while there was an interaction between time and group (male rat: Wald χ2=15.874, P=0.001; Wald χ2=9.460, P=0.024). There were significant differences in the rat liver weight and liver coefficient in each group (male rat: F=18.964 and 29.968, both P<0.001; female rat: F=11.919 and 15.070, both P<0.001), with the lowest liver weight (10.17±1.15) g and liver coefficient (1.99±0.21)% measured in male rats in the high-dose group, and the highest liver weight (12.91±1.29) g and liver coefficient (4.10±0.56)% in female rats in the high-dose group. The median urine arsenic levels (interquartile range) were 25.60 (30.27), 146.56 (101.06), 1 034.68 (600.06) and 3 796.98 (19 966.89) μg/L in rats in the control, low-dose, medium-dose and high-dose groups, respectively (χ2=50.211, P<0.001), and the urine arsenic level was significantly higher in the medium- and high-dose groups than in the control group (both P<0.001). Hepatic edema was seen in rats in the low- and medium-dose groups, and hepatic edema, focal hepatic cell necrosis, hyperplasia of bile capillaries and peri-bile capillary endolysis were observed in rats in the high-dose group. Conclusions Chronic exposure to arsenic may cause morphological alterations of rat hepatic tissues, and the rat hepatic damage aggravates with the dose of exposure to arsenic.

Objective:To learn about the arsenic status of drinking water in Urumqi City and evaluate its health risk, so as to provide scientific basis for the construction of water improvement projects in Urumqi City.Methods:From 2018 to 2020, 687 water samples were collected at monitoring sites in 7 districts and 1 county of Urumqi City for three consecutive years, and arsenic in drinking water was detected according to "Standard Examination Methods for Drinking Water - Nonmetal Parameters" (GB/T 5750.5-2006), and the arsenic in drinking water was evaluated according to "Standards for Drinking Water" (GB/T 5749-2006). The health risk of arsenic in drinking water in Urumqi City was evaluated by using the health risk assessment model recommended by United States Environmental Protection Agency (USEPA).Results:All of 687 water samples were centralized water supply, the arsenic compliance rates in dry season ( n = 342) and wet season ( n = 345), surface water ( n = 414) and underground water ( n = 273) were 100.0%. In dry season, the carcinogenic risk of arsenic via drinking water was 8.24 × 10 -6/a. In wet season, the carcinogenic risk of arsenic via drinking water was 3.30 × 10 -6/a. Conclusions:Remarkable achievements have been made in the construction of water improvement projects in Urumqi City, and the drinking water arsenic condition is good, the health risk of arsenic via drinking water is small. In the future, we should continue to strengthen the monitoring of drinking water quality, promote the construction of water improvement projects, further improve the drinking water sanitation, and put forward targeted prevention and control measures to ensure drinking water safety.

Objective:To study the effect of insulin intraperitoneal injection on abnormal blood lipid intype 2 diabetic KKAy mice.Methods:Type 2 diabetic mice model was established by feeding high fat and high sugar diet. KKAy model mice were randomly divided into intraperitoneal injection group ( n=6), subcutaneous injection group ( n=6) and no-treatment group ( n=3). At the same time, healthy C57BL/6J mice were selected as normal group ( n=6), and healthy KKAy mice as disease-free group ( n=6). The treatment process was divided into two stages. The first stage consists of 6 weeks, in which the mice in the intraperitoneal and subcutaneous groups were treated with insulin intraperitoneally and subcutaneously respectively. The second stage consists of 4 weeks, in which the mice in intraperitoneal and subcutaneous groups were subcutaneously injected with insulin. The mice in the remaining 3 groups were not treated. The changes of related indicators were detected every two weeks, including body weight, fasting blood sugar, 2 hours after meal blood sugar, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Results:Changing the injection solution in the medium term of the treatment had no effect on the body mass and blood sugar of KKAy mice with type 2 diabetes. Under this condition, the effect of intraperitoneal injection of insulin on HDL-C and LDL-C is significantly better than that of subcutaneous injection. Besides, both injection solutions are effective in regulating TG, but the effect of reducing total cholesterol is not obvious.Conclusions:The intraperitoneal injection of insulin has a certain effect on the blood lipid abnormality of type 2 diabetic KKAy mice. It can promote the increase of HDL-C, the decrease of LDL-C, and the decrease of TG.

Under normal conditions,insulin secreted by the pancreas enters the liver through the portal vein,forming a difference in insulin concentration above the peripheral circulation.Subcutaneous administration of insulin forms a portal-peripheral concentration gradient of insulin above the liver,which is inconsistent with normal physiological conditions.Intraperitoneal insulin administration has been extensively investigated because that is closer to physiological state.In this paper,the pharmacokinetic and pharmacodynamic studies of insulin intraperitoneal administration were reviewed.Compared with the conventional subcutaneous delivery,intraperitoneal insulin administration can not only reduce the incidence of hypoglycemia,but also has the advantage of correcting abnormal lipid metabolism.This means that intraperitoneal administration of insulin has a positive effect on the prevention and treatment of diabetic complications.Therefore,it is necessary and feasible to develop a safe,low-cost,and easy-to-use percutaneous intraperitoneal insulin delivery device.