Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Objective:To explore the risk factors related to the formation of parastomal hernia (PSH) in patients with colorectal cancer after preventive ileostomy, provide Evidence-based medicine basis for prevention and treatment, and reduce the incidence of incision hernia (SSIH) at the stoma.Methods:The clinical data of 214 patients who underwent laparoscopic radical resection of colorectal cancer combined with preventive loop ileostomy in the General Surgery Department of the Linyi People′s Hospital from January 2019 to May 2021 were retrospectively analyzed. The incidence of PSH was statistically analyzed, and the risk factors of PSH were analyzed by binary logistic regression.Results:There were 177 cases of PSH in 214 patients, with an incidence rate of 82.71%. There were 5 cases of SSIH (2.34%). The results of single factor analysis showed that there were significant differences in body mass index (BMI), postoperative diversion time and the proportion of stoma through rectus abdominis muscle between the PSH group and the non PSH group (all P<0.05); The results of binary logistic regression analysis showed that BMI, postoperative diversion time, rectus abdominis muscle stoma, incision infection and liquefaction were important influencing factors for the formation of PSH after preventive loop ileostomy for colorectal cancer (all P<0.05). Conclusions:BMI, postoperative diversion time, rectus abdominis muscle stoma, incision infection and liquefaction are important influencing factors for the formation of PSH after preventive ileostomy. Intervention measures can be targeted to reduce the incidence of SSIH by reducing the risk of PSH.

BACKGROUND/OBJECTIVES: This study examined the relationship between famine exposure in early life and the risk of type 2 diabetes in adulthood during the 1959–1961 Chinese Famine. SUBJECTS/METHODS: A total of 3,418 individuals aged 35–74 years free of diabetes from two studies in 2006 and 2009 were followed up prospectively in 2009 and 2012, respectively. Famine exposure was classified as unexposed (individuals born in 1962–1978), fetal exposed (individuals born in 1959–1961), child exposed (individuals born in 1949–1958), and adolescent/adult exposed (born in 1931–1948). A logistic regression model was used to assess the relationship between famine exposure and diabetes after adjustment for potential covariates. RESULTS: During a three-year follow-up, the age-adjusted incidence rates of type 2 diabetes were 5.7%, 14.5%, 12.7%, and 17.8% in unexposed, fetal-exposed, child-exposed, and adolescent/adult-exposed groups, respectively (P < 0.01). Relative to the unexposed group, the relative risks (95% confidence interval) for diabetes were 2.15 (1.29–3.60), 1.53 (0.93– 2.51), and 1.65 (0.75–3.63) in the fetal-exposed, child-exposed, and adolescent/adult-exposed groups, after controlling for potential covariates. The interactions between famine exposure and obesity, education level, and family history of diabetes were not observed, except for the urbanization type. Individuals living in rural areas with fetal and childhood famine exposure were at a higher risk of type 2 diabetes, with relative risks of 8.79 (1.82–42.54) and 2.33 (1.17–4.65), respectively. CONCLUSIONS These findings indicate that famine exposure in early life is an independent predictor of type 2 diabetes, particularly in women. Early identification and intervention may help prevent diabetes in later life.

Humans ; East Asian People ; Surveys and Questionnaires ; Vitiligo/epidemiology*

Objective:To explore the differences of risk stratification of very high-risk or extreme high-risk atherosclerotic cardiovascular diseases (ASCVD) and the attainment rates of low-density lipoprotein cholesterol (LDL-C) management targets evaluated by three different criteria, and the causal attributions of these differences.Methods:Patients with ASCVD were consecutively enrolled from January 1 to December 31 in 2019, and were evaluated for very high-risk or extreme high-risk and LDL-C goal attainment rates with 2018 American guideline on the management of blood cholesterol (2018AG), 2019 China Cholesterol Education Program (CCEP) Expert Advice for the management of dyslipidemias (2019EA) and 2020 Chinese expert consensus on lipid management of very high-risk ASCVD patients(2020EC), respectively. The causal attributions of the differences in attainment rates were analyzed as well.Results:A total of 1 864 ASCVD patients were included in this study. According to 2018AG, 2019EA and 2020EC, the proportions of the patients with very high-risk or extreme high-risk were 59.4%, 90.7%, and 65.6%, respectively. The absolute LDL-C target attainment rates were 37.2%, 15.7%, and 13.7%, respectively, the differences between each two rates were statistically significant (all P<0.001). As to the differences in attainment rates between 2020EC and 2018AG, 61.5% were due to the different LDL-C goal attainment values and 38.5% were caused by the different risk stratifications, while for the differences between 2020EC and 2019EA attainment rates, different LDL-C goal attainment values were responsible for 13.2%, and different risk stratifications were responsible for 86.8% of the differences. Conclusions:There are significant differences in the proportions and LDL-C attainment rates among the three different criteria for very high-risk or extreme high-risk ASCVD. 2020EC showed a moderate proportion of patients with extreme high-risk, and had the lowest LDL-C attainment rate. The differences between 2020EC and 2018AG are mainly due to the LDL-C target values, and the differences between 2020EC and 2019EA are mainly caused by the risk stratifications.

Objective:To evaluate the biosafety of medical injectable carboxymethyl glycosaminoglycan gel.Methods:Ames test, chromosome aberration test in vitro and gene mutation test in vitro were used to detect the genotoxicity of the medical carboxymethyl glycosaminoglycan gel. The gel saline extract (50 ml/kg) was injected slowly through the marginal vein of the ear into Japanese big-eared rabbits. The body temperature was measured and the temperature rise was calculated. The gel saline extract (50 ml/kg) and normal saline (control) were injected intraperitoneally and intravenously into the Kunming mice, respectively. The toxicity response in mice was observed after injection, and bodyweight change was valued. The gel saline extract, normal saline and distilled water were added into the rabbit anti-clotting, to detect the rate of hemolysis.Results:Under active and inactive conditions, the number of spontaneous revertants of the 4 strains of gel saline extract group and gel DMSO extract group did not reach 2 times of that of the corresponding negative control group. The rate of chromosome aberration of the three dose groups were 0. There was no significant increase in the large colony mutation frequency, small colony mutation frequency and total mutation frequency in three dose groups (all P>0.05). After injection of gel saline extract for 24, 48 and 72 h, no toxic reaction was found in each group of mice. With the extension of time after injection, the body weight of mice in the sample group and the control group increased, but the difference was not statistically significant ( P>0.05). After injection of gel saline extract, the temperature rise of 3 Japanese big-eared rabbits were 0.0, 0.3 and 0.2 ℃ respectively. The results of hemolysis test showed that the hemolysis rate of the polycarboxymethyl glucosamine gel was 0.1%. Conclusions:No genetic toxicity changes were found in carboxymethyl glycosaminoglycan to induce gene mutation or chromosome damage in bacteria and cells, and no pyrogenicity, acute systemic toxicity and hemolysis were observed. These results indicate that thecarboxymethyl glycosaminoglycan gel has good biosafety.

BACKGROUND: The injectable carboxymethyl glycosaminoglycan anti-adhesion gel prepared in the previous study combines the advantages of anti-adhesion membrane and anti-adhesion liquid. It can form soft gel in situ in a relatively short time, which is not affected by body position, bear the pressure of surrounding tissues and can be used without compression. OBJECTIVE: To evaluate the biocompatibility of medical injectable carboxymethyl glycosaminoglycan anti-adhesion gel. METHODS: Logarithmic growing L929 cells were used as test cells, and the cytotoxicity of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract was detected by MTT method. The intradermal stimulation test of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract was carried out in Japanese big ear rabbits. Guinea pigs were used as experimental animals to carry out intradermal induction and local induced delayed hypersensitivity test of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract. Wistar rats were used as experimental animals to carry out the subchronic toxicity test of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract. RESULTS AND CONCLUSION: The cytotoxicity of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract was grade 1, meeting the standard requirements. Injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract had no potential intradermal stimulation and no potential skin sensitization. In the subchronic toxicity test, the rats were subjected to the tail vein injection of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract for 28 continuous days, and there was no obvious subchronic systemic toxicity in body mass, hematology, coagulation function, blood biochemistry and visceral pathology. These results indicate that the injectable carboxymethyl glycosaminoglycan anti-adhesion gel has good biosafety.

Objective: To investigate the protective effect of intraperitoneal transplantation of human liver-derived stem cells at different times against concanavalin A (ConA)-induced acute liver injury in mice. Methods: A total of 88 male C57BL/6 mice were randomly divided into normal control group (group C), ConA model group (group M), and human liver-derived stem cells (HYX1)+ConA group (group E); according to the interval between phosphate buffer/HYX1 injection and ConA injection, Groups M and E were further divided into 3-hour groups (M1 and E1 groups), 6-hour groups (M2 and E2 groups), 12-hour groups (M3 and E3 groups), 24-hour groups (M4 and E4 groups), and 48-hour groups (M5 and E5 groups). The levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and total bilirubin (TBil) in peripheral blood were measured, liver tissue sections were used to observe pathological changes, and the Ishak score for liver inflammation was determined. The independent samples t-test was used for comparison between groups, and P < 0.05 was considered statistically significant. Results: The levels of ALT, AST, and TBil in group C were (36.25±1.16) U/L, (120.20±5.77) U/L, and (2.20±0.23) μmol/L, respectively; the levels of ALT, AST, and TBil and Ishak score were (8 721.23±837.39) U/L, (8 110.31±290.10) U/L, (8.41±0.10) μmol/L, and (13.32±1.30), respectively, in group M1, (8 334.31±666.50) U/L, (7 560.20±760.34) U/L, (10.40±0.80) μmol/L, and (12.67±0.81), respectively, in group M2, (8 960.75±551.93) U/L, (8 535.62±675.14) U/L, (10.95±1.43) μmol/L, and (14.57±0.65), respectively, in group M3, (8 618.57±886.40) U/L, (11 440.54 ± 1 327.86) U/L, (13.30±1.86) μmol/L, and (13.21±1.06), respectively, in group M4, and (10 170.13±1 112.37) U/L, (11 470.56±1 108.40) U/L, (12.75±1.55) μmol/L, and (15.07±1.58), respectively, in group M5. The levels of ALT, AST, and TBil and Ishak score were (1 016.35±163.47) U/L, (952.30±103.91) U/L, (7.77±0.62) μmol/L, and (3.50±0.21), respectively, in group E1, (42.10±6.20) U/L, (126.72±13.33) U/L, (3.41±0.53) μmol/L, and (2.01±0.40), respectively, in group E2, (44.21±4.30) U/L, (216.71±35.88) U/L, (3.47±0.44) μmol/L, and (2.13±0.25), respectively, in group E3, (2 909.69±212.14) U/L, (2 988.43±333.70) U/L, (7.03±0.93) μmol/L, and (4.70±0.50), respectively, in group E4, and (7 874.26±799.60) U/L, (10 940.54±947.35) U/L, (10.53±1.09) μmol/L, and (8.60±0.83), respectively, in group E5. Groups M1-M5 had significantly higher levels of ALT, AST, and TBil than group C (all P < 0.01), and groups M1-M4 had significantly higher levels of AST and ALT than groups E1-E4 (all P < 0.01), while there were no significant differences in the levels of AST and ALT between groups M5 and E5 (both P > 0.05). The pathological sections of liver tissue showed that compared with group M, group E had significant reductions in the degree of necrosis and Ishak score (both P < 0.05). Conclusion Intraperitoneal transplantation of human liver-derived stem cells has a protective effect against ConA-induced acute liver injury in mice, and the injection at 6 and 12 hours in advance has the best protective effect.