Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Heterotypic cell-in-cell structures(heCICs)mediate unique non-autonomous cell death,which are widely involved in a variety of important pathological processes,such as tumorigenesis,pro-gression and clinical prognosis.Methylenetetrahydrofolata dehydrogenase 2(MTHFD2),one of the key enzymes of one-carbon metabolism,is highly expressed in a variety of tumor cells.In this study,in order to investigate the effect of MTHFD2 on the formation of heCICs,liver cancer cells and immune cells were first labeled separately by live cell dyes,and the heCIC model was established by using fluorescence mi-croscopy for cell imaging and analysis.After transiently knocking down MTHFD2 in cells by RNAi,we found that the ability of PLC/PRF/5 and Hep3B to form heCICs with immune cells was significantly in-creased(all P＜0.01).MTHFD2 recombinant expression plasmid was constructed by the homologous re-combination method,and MTHFD2 overexpression cell lines were further constructed.Then,the effect of MTHFD2 overexpression on the ability to form heCICs was detected by co-culturing the overexpression cell lines with immune cells.The results showed that the rate of heCIC formation was significantly re-duced after overexpression of MTHFD2(all P＜0.001).In conclusion,this study demonstrated that MTHFD2 is a negative regulator of heCIC formation,providing a research basis for targeting MTHFD2 to promote heCIC formation and enhance the in-cell killing of immune cells.

This study adopted the policy text analysis method,review the historical background of the enactment,aimed to comparatively analyze the international pharmaceutical trade policies of the BRICS countries.The main objectives of the BRICS countries'international pharmaceutical trade policies included ensuring stable and accessible drug supply,expanding exports of domestic products and creating a favorable political environment.For these purposes,Brazil,Russia,and South Africa all ensure drug supply through substantial imports.However,they have also taken measures such as compulsory patent licensing and promoting localization of production by foreign companies to reduce import dependence.India,on the other hand,protects its domestic industry by resisting drug imports to ensure drug supply while simultaneously promoting the export of pharmaceutical products.China continually optimizes approval and data monitoring procedures to align with international standards,creating a favorable trade environment and expanding exports.China should further refine its international pharmaceutical trade policies while ensuring the autonomy of domestic drug research and supply,fostering stronger collaboration within BRICS nations and promoting global access to public healthcare products.

OBJECTIVE: To analyze the association between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years, and to provide suggestions for the prevention and control of metabolic syndrome in Chinese children and adolescents. METHODS: Data were collected from the research project "Development and Application of Technology and Related Standards for Prevention and Control of Major Diseases among Students" of public health industry in 2012. This project is a cross-sectional study design. A total of 65 347 students from 93 primary and secondary schools in 7 provinces including Guangdong were selected by stratified cluster random sampling method. Given the budget, 25% of the students were randomly selected to collect blood samples. In this study, 10 176 primary and middle school students aged 7 to 17 years with complete physical measurements and blood biochemical indicators were selected as research objects. Chi-square test was used to compare the distribution differences of growth patterns under different demographic characteristics. Birth weight, waist circumference and blood biochemical indexes were expressed in the form of mean ± standard deviation, and the differences among different groups were compared by variance analysis. Binary Logistic regression model was used to analyze the relationship between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years. RESULTS: The prevalence of metabolic syndrome in children and adolescents was 6.56%, 7.18% in boys and 5.97% in girls. The risk of metabolic syndrome was higher in the catch-down growth group than in the normal growth group (OR=1.417, 95%CI: 1.19-1.69), and lower in the catch-up growth group(OR=0.66, 95%CI: 0.53-0.82). After adjusting for gender, age and so on, the risk of developing metabolic syndrome in the catch-down growth group was higher than that in the normal growth group (OR=1.25, 95%CI: 1.02-1.52), but there was no significant difference between the catch-up growth group and the normal growth group (OR=0.79, 95%CI: 0.62-1.01). Stratified analysis showed that the association between different growth patterns and metabolic syndrome was statistically significant in the 7-12 years group, urban population, and Han Chinese student population. CONCLUSION There is a correlation between different growth patterns and metabolic syndrome in children and adolescents. The risk of developing metabolic syndrome in children and adolescents with catch-down growth is higher than that in the normal growth group, which suggests that attention should be paid to the growth and development of children and adolescents, timely correction of delayed growth and prevention of adverse health outcomes.
Male ; Female ; Humans ; Child ; Adolescent ; Metabolic Syndrome/epidemiology* ; Cross-Sectional Studies ; Students ; Urban Population ; Asian People ; China/epidemiology* ; Prevalence

OBJECTIVE: To investigate the status of depression and social anxiety in children and adolescents, and to analyze the association between body fat distribution and depression, social anxiety in children and adolescents. METHODS: A total of 1 412 children aged 7 to 18 years in Beijing were included by stratified cluster random sampling method. Body fat distribution, including total body fat percentage (total BF%), Android BF%, Gynoid BF% and Android-to-Gynoid fat ratio (AOI), were obtained by dual-energy X-ray absorption method. Depression and social anxiety were evaluated by Children Depression Inventory and Social Anxiety Scale for Children. Multivariate linear regression and restricted cubic spline analysis were used to estimate the linear and non-linear correlation between body fat distribution and depression and social anxiety. RESULTS: 13.1% and 31.1% of the children and adolescents had depressive symptoms and social anxiety symptoms respectively, and the detection rate of depression and social anxiety in the boys and young groups was significantly lower than those in the girls and old groups. There was no significant linear correlation between total BF%, Android BF%, Gynoid BF%, AOI and depression and social anxiety in the children and adolescents. However, total BF% and Gynoid BF% had significant nonlinear correlation with depression, showing an inverted U-shaped curve relationship with the tangent points of 26.8% and 30.9%, respectively. In terms of the nonlinear association of total BF%, Android BF%, Gynoid BF% and AOI with depression and social anxiety, the change trends of the boys and girls, low age group and high age group were consistent. The overall anxiety risk HR of body fat distribution in the boys was significantly higher than that in the girls, and the risk HR of depression and social anxiety were significantly higher in the high age group than those in the low age group. CONCLUSION There was no significant linear correlation between body fat distribution and depression and social anxiety in children and adolescents. Total BF% and depression showed an inverted U-shaped curve, mainly manifested in Gynoid BF%, and this trend was consistent in different genders and different age groups. Maintaining children and adolescents' body fat distribution at an appropriate level is the future direction of the prevention and control of depression and social anxiety in children and adolescents.
Humans ; Female ; Child ; Male ; Adolescent ; Cross-Sectional Studies ; X-Rays ; Depression/epidemiology* ; Absorptiometry, Photon/methods* ; Body Mass Index ; Body Fat Distribution ; Anxiety/epidemiology* ; Adipose Tissue ; Body Composition

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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Objective:To investigate the impact of recombinant human epidermal growth factor (rh-EGF) on the epithelial recovery and the tear film stability after trans-epithelial corneal collagen crosslinking in patients with progressive keratoconus.Methods:A randomized controlled clinical trail was designed.Consecutive 66 patients (37 males and 29 females) with an average age of (21.27±3.80) years old diagnosed with primary progressive keratoconus and hospitalized in Xiamen Eye Center Affiliated to Xiamen University from October, 2016 to January, 2017 were enrolled and treated with unilateral enhanced transepithelial corneal crosslinking surgery by iontophoresis, and the patients were randomly divided into control group and experimental group according to random number table method, with 33 patients 33 eyes in each group.The eyes in the control group were treated with carboxy-methylcellulose sodium lubricant eye drops and the eyes in the experimental group were treated with rh-EGF eye drops.The ocular surface disease index (OSDI) questionare, slit lamp examination, Schirmer Ⅰ test, corneal fluorescein sodium staining scoring, non-contact tonometry, uncorrected visual acuity, best corrected visual acuity, bulbar conjunctival congestion scoring, lacrimal sevretion test, non-invasive break-up time of tear film (NIBUT), as well as tear meniscus height analysis were performed before surgery, and on day 1, day 3, day 5, day 7, day 14 and day 28 after surgery.This study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xiamen Eye Center Affiliated to Xiamen University (No.2016-ME-003).Results:On day 7 after surgery, the OSDI values were increased in both groups than the preoperative value, while the value in the experimental group was significantly lower than that in the control group ( P<0.05). There were statistically significant differences in the overall corneal epithelial staining score values between the two groups at different time points ( Fgroup=16.701, P<0.01; Ftime=454.418, P<0.01). The corneal epithelial staining score in the experimental group on day 3 and day 5 after surgery were significantly lower than those in the control group (1.79±0.65 vs. 2.70±0.68; 0.91±0.46 vs. 1.55±0.51) (both at P<0.01). The conjunctival congestion score in the experimental group was significantly lower than that of the control group on day 3 and day 5 after surgery (both at P<0.05). There were statistically significant differences in the overall NIBUT values between the two groups at different time points ( Fgroup=13.084, P<0.01; Ftime=34.383, P<0.01). The NIBUT values were significantly decreased rapidly on day 7, day 14 and day 28 after surgery in both groups (all at P<0.01), but gradually recovered.The NIBUT of the experimental group on day 7 and day 14 after surgery were significantly higher than those of the control group ([8.18±2.26]seconds vs. [5.93±2.33]seconds; [9.49±1.95]seconds vs. [7.52±2.27]seconds) (both at P<0.01). No statistical differences were found in the tonometry value, visual acuity, value of Schirmer I test as well as tear meniscus height at any time point before or after surgery between the two groups (all at P>0.05). Conclusions:Recombinant human epidermal growth factor has positive effects in the patients received enhanced transepithelial corneal crosslinking surgery, presenting with promotion of epithelial healing, relief of post-operative discomfort, and the recovery of tear film stability.

Objective To analyze the burden of intestinal infectious diseases in Jining city from 2009 to 2016, determine the epidemic trends and the high-risk groups in this area, so as to provide evidence for the prevention and control of intestinal infectious diseases. Methods The intestinal infectious diseases case information were collected from the Infectious Diseases Surveillance Information Reporting System. Based on these data, the incidence rate, the years lived with disability (YLDs) and the intensity of YLDs of intestinal infectious diseases was calculated. Results From 2009 to 2016, the annual incidence rate of intestinal infectious diseases in Jining city was 128.81/100 000, the annual incidence rate of subtype diseases in the descending order were other infectious diarrhea (74.74/100 000), hand-foot-and-mouth disease (49.15/100 000), bacillary dysentery (3.65/100 000), hepatitis E (0.57/100 000), acute hemorrhagic conjunctivitis (0.37/100 000) and hepatitis A (0.34/100 000). The highest incidence of intestinal infectious diseases was at May to August. The total YLDs caused by intestinal infectious diseases were 593.04 person-years, including 372.31 person-years for males and 220.73 person-years for females. The YLDs ranked in descending order were of hand-foot-mouth disease (326.88 person-years), other infectious diarrhea (235.74 person-years), hepatitis E (10.65 person-years), bacillary dysentery (10.09 person-years), hepatitis A (7.71 person-years), and acute hemorrhagic conjunctivitis (1.97 person-years), and the corresponding intensity of YLDs were 0.489, 0.353, 0.016, 0.015, 0.012, and 0.003 person-years /100 000, respectively. Conclusions The hand-foot-and-mouth disease and the other infectious diarrhea were the main intestinal infectious diseases subtypes prevailed in Jining city from 2009 to 2016, whose incidence was highest in the season of summer, and the preschool children and elderly people were the high-risk populations. According to its incidence characteristic, relevant government departments can take effective measures to prevent and control the intestinal infectious diseases in Jining city.

The aim of this study was to investigate the renal toxicity of rhubarb and its mechanism. The SD rats were randomly divided into three groups: normal group and two rhubarb extract groups (16, 2 g·kg⁻¹). According to the dose conversion method between human and animal, rhubarb 16 g·kg⁻¹ and 2 g·kg⁻¹ were equivalent to 10 times and 1.25 times of human clinical dose respectively. Rhubarb extract was administered by a gastric gavage to rats once daily for 30 days. Serum urea nitrogen （BUN）, creatinine （CRE） and urine KIM-1, NGAL and renal morphology were analyzed. The expressions of OAT1, OAT3 and clusterin mRNA in kidney were measured. The results showed that the low dose of rhubarb had no obvious renal toxicity. The high dose group showed mild and moderate renal injury and a down-regulation of clusterin mRNA expression in the kidney tissue. The renal toxicity in male animals was heavier than that in female animals. There was no significant change in blood BUN and CRE in the high dose group. But urine NGAL level of the high dose group increased by 51.53% compared with normal group, of which male animals increased more significantly (<0.05, compared with the normal group). The expressions of renal OAT1 and OAT3 mRNA in the low dose group were obviously higher than that in the normal group. The results indicated that the high dose of rhubarb could cause the renal toxicity. The dosage should be controlled reasonably in the clinical use. OAT1 and OAT3 mRNA related to anionic transport in kidney tissue played a compensatory protective role in rhubarb-induced renal injury. But the compensatory effect is relatively weak at the high dose level. In addition, routine renal function indicators BUN and CRE had limitation for monitoring the kidney toxicity of rhubarb. It is suggested that urine NGAL detection might be helpful for monitoring the renal toxicity of rhubarb.

OBJECTIVETo observe the protective effects of potassium channel opener nicorandil against cognitive dysfunction in mice with streptozotocin (STZ)-induced diabetes.

METHODSC57BL/6J mouse models of type 1 diabetes mellitus (T1DM) were established by intraperitoneal injection of STZ and received daily treatment with intragastric administration of nicorandil or saline (model group) for 4 consecutive weeks, with normal C57BL/6J mice serving as control. Fasting blood glucose level was recorded every week and Morris water maze was used to evaluate the cognitive behavior of the mice in the 4th week. At the end of the experiment, the mice were sacrificed to observe the ultrastructural changes in the hippocampus and pancreas under transmission electron microscopy; the contents of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the hippocampus and SOD activity and MDA level in the brain tissue were determined.

RESULTSCompared with the control group, the model group showed significantly increased fasting blood glucose (P<0.001), significantly prolonged escape latency (P<0.05) and increased swimming distance (P<0.01) with ultrastructural damage of pancreatic β cells and in the hippocampus; GIP and GLP-1 contents in the hippocampus (P<0.01) and SOD activity in the brain were significantly decreased (P<0.05) and MDA content was significantly increased in the model group (P<0.05). Compared with the model group, nicorandil treatment did not cause significant changes in fasting blood glucose, but significantly reduced the swimming distance (P<0.05); nicorandil did not improve the ultrastructural changes in pancreatic β cells but obviously improved the ultrastructures of hippocampal neurons and synapses. Nicorandil also significantly increased the contents of GIP and GLP-1 in the hippocampus (P<0.05), enhanced SOD activity (P<0.05) and decreased MDA level (P<0.01) in the brain tissue.

CONCLUSIONNicorandil improves cognitive dysfunction in mice with STZ-induced diabetes by increasing GIP and GLP-1 contents in the hippocampus and promoting antioxidation to relieve hippocampal injury.