Background and aims:Environmental pollutants,particularly organochlorine insecticides like endosulfan(ENDO),are increasingly linked to liver toxicity and related diseases.Despite its widespread historical use,the mechanisms underlying ENDO-induced liver damage remain poorly understood.This study aims to elucidate the cellular and molecular mechanisms of ENDO-induced hepatotoxicity.Methods:C57BL/6 mice were exposed to ENDO for two weeks.Single-cell RNA sequencing(scRNA-seq)was subsequently performed on mouse livers to explore ENDO-induced hepatotoxicity at the single-cell level.Differentially expressed genes(DEGs)across cell types and treatments were identified and then subjected to pathway enrichment to uncover key biological processes affected by ENDO.Transcription factor(TF)regulatory network,pseudotime trajectory,and cellular communication analysis were used to explore the molecular and cellular changes after ENDO exposure.Results:ENDO not only caused direct hepatocyte injury but also activated hepatic stellate cells and lymphocytes,triggering inflammatory responses with upregulation of multiple key chemokines and cytotoxic genes.Additionally,ENDO exposure led to the recruitment and activation of myeloid cells,contributing to the inflammatory milieu.An increase in intercellular communication and changes to the hepatic microenvironment,especially the interaction between activated hepatic stellate cells and CD8+T cells were observed,further implicating these processes in ENDO-induced liver damage.Conclusions:This study provides new insights into the cellular and molecular mechanisms underlying liver injury induced by organochlorine insecticides like ENDO.Key genes and pathways involved in ENDO-associated liver toxicity have been identified at a single-cell resolution.These findings suggest that altered cellular communications and inflammatory responses may play pivotal roles in the pathogenesis of ENDO-induced liver injury.

OBJECTIVE To explore the mechanism of Baihe Dihuang decoction in the treatment of Alzheimer's disease(AD) based on network pharmacology, molecular docking and animal experiment. METHODS TCMSP were used to predict the active components and targets of Baihe Dihuang decoction and disease-related targets were collected from GeneCards, OMIM and DRUGBANK databases, respectively. Target protein interactions were analyzed with STRING database and biological function and pathway were analyzed with Metascape database. Lastly relevant results were analyzed with Cytoscape 3.8.0. AutoDock vina software was used for molecular docking to analyze the binding energy of the active components and key targets of Baihe Dihuang decoction. PyMOL software were used to visualize the optimal docking results. ICR male mice were randomly divided into control group, model group, Rolipram group, low, medium and high dose group of Baihe Dihuang decoction. After 14 days of administration, the neurobehavioral scores of mice in each group were collected, and the expression of related proteins in brain tissue was detected, ELISA and Western blotting were used to detect the expression of the key protein cAMP, PKA, p-CREB and BDNF. At last, the adverse reaction of Baihe Dihuang decoction was observed by vomiting experiment. RESULTS A total of 13 active components and 39 key targets were collected from network pharmacology. The docking results showed that the first 10 core targets all performed well and their effects were closely related to PRKACA. Compared with the control group, the model group mice's recognition rate of new objects and the spontaneous alternation reaction rate were significantly reduced, the escape latency was significantly prolonged, and the target quadrant stay time, the number of crossing platforms were significantly reduced; cAMP, PKA, p-CREB and BDNF in the hippocampus of mice was significantly decreased. Baihe Dihuang decoction could reverse the behavior of AD mice and the expression of cAMP, PKA, p-CREB and BDNF. In the vomiting experiment, the anesthesia recovery time of the Rolipram group was significantly prolonged, while that of the Baihe Dihuang decoction group was not significantly affected. CONCLUSION The mechanism of Baihe Dihuang decoction in the treatment of AD may be related to its influence on cAMP-PKA and regulation of cAMP-PKA-CREB-BDNF signal pathway, and the adverse reactions are milder than those of clopramide.

Objective To predict the mechanism of Chaihu Shugan Powder against depression based on network pharmacology and molecular docking technology;To verify them through animal experiment of chronic unpredictable mild stress(CUMS)depression model rats.Methods TCMSP was used to screen the active components of Chaihu Shugan Powder and the related targets were obtained.Disease targets were retrieved by DisGeNET,GeneCards and GEO databases.The protein-protein interaction(PPI)network construction,GO and KEGG pathway enrichment analyses were conducted to determine the action pathway of Chaihu Shugan Powder against depression.Molecular docking of main active components and potential targets was performed.The depression model was established by CUMS combined with solitary rearing method,in which Chaihu Shugan Powder and PI3K specific inhibitor LY294002 were used to intervene depression model rats.Western blot and qPCR were respectively used to detect the action pathway related proteins and mRNAs.ELISA was used to detect the contents of monoamine neurotransmitters 5-HT and NE in hippocampal tissue,and their pathways of action were integrated and analyzed.Results Totally 118 active components of Chaihu Shugan Powder against depression and 74 potential targets were screened;KEGG pathway enrichment analysis indicated that action pathway of Chaihu Shugan Powder against depression were closely related to PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,etc.Molecular docking showed that quercetin,kaempferol,β-sitosterol,isorhamnetin,naringenin had good binding activity with AKT1,PIK3CA,GSK3B,IL6,IL1B.The animal experiments showed that Chaihu Shugan Powder could improve the depression-like behavior of model rats,increase the phosphorylation levels of PI3K and Akt in hippocampal tissue,down-regulate the expression of GSK3β,and increase the contents of 5-HT and NE.LY294002 could reverse the effect of Chaihu Shugan Powder.The results of integration analysis showed that PI3K/Akt signaling pathway of Chaihu Shugan Powder was closely related to metabolism of 5-HT and NE.Conclusion Chaihu Shugan Powder can exert antidepressant effects by activating the PI3K/Akt signaling pathway,inhibiting the expression of GSK3β,and increasing the levels of monoamine neurotransmitters 5-HT and NE.

Objective:To explore the efficacy and safety of different anti-platelet regimens in the treatment of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) guided by point-of-care testing of CYP2C19 gene. Methods:A single-centre, prospective, randomised, open-label, and blinded endpoint design was uesd in the study. From July 2020 to January 2022, HR-NICE patients were enrolled in the Stroke Green Channel and Department of Neurology of Xuzhou Central Hospital, and all patients were scraped the buccal mucosa for screening for CYP2C19 loss-of-function allele carriers by point-of-care testing . Patients with intermediate metabolism were defined as those who carried 1 loss-of-function allele and patients with poor metabolism were those who carried 2 loss-of-function alleles. This study reduced the test turnaround time to 1 hour by using a fully automated medical polymerase chain reaction analyzer for a point-of-care test of CYP2C19 genotype. CYP2C19 loss-of-function allele carriers were divided according to the random number table method into the conventional treatment group (clopidogrel 75 mg, once a day), the ticagrelor group (ticagrelor 90 mg, twice a day) and the intensive dose group (clopidogrel 150 mg, once a day) separately combined with aspirin (100 mg, once a day) dual antiplatelet for 21 days. Baseline information, Acute Stroke Org 10172 Treatment Trial staging, 90-day modified Rankin Scale score, occurrence of adverse events and severe adverse events were collected for all the 3 groups. The primary efficacy outcome was new stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days. Results:A total of 716 patients were included: 240 in the conventional treatment group, 240 in the ticagrelor group and 236 in the intensive dose group. There was no statistically significant difference between the 3 groups at baseline (all P>0.05). There were 26 cases (10.8%) with new stroke events in the conventional treatment group, 11 cases (4.6%) in the ticagrelor group and 4 cases (1.7%) in the intensive dose group, with statistically significant differences among the 3 groups (χ 2=19.28, P<0.05), and the differences between the conventional treatment group and the ticagrelor group (χ 2=6.59, P=0.010) and between the conventional treatment group and the intensive dose group (χ 2=16.83, P<0.001) were statistically significant, whereas the difference between the ticagrelor group and the intensive dose group was not statistically significant ( P>0.05). In the 3 groups, there was 1 case (0.4%) of severe bleeding in the conventional treatment group, 6 cases (2.5%) in the ticagrelor group and none in the intensive dose group, which showed statistically significant differences (χ 2=7.23, P<0.05), and there was statistically significant difference between the ticagrelor group and the intensive dose group ( P=0.030). Among the patients with intermediate CYP2C19 metabolism, there were 13 cases (13/158, 8.2%) with 90-day recurrent stroke in the conventional treatment group, 4 cases (4/153, 2.6%) in the ticagrelor group, and 0 case (0/159) in the intensive dose group, with statistically significant difference (χ 2=16.04, P<0.001), and the differences between the intensive dose group and the conventional treatment group were statistically significant (χ 2=13.64, P<0.001), whereas there was no statistically significant difference between the intensive dose group and the ticagrelor group ( P>0.05). In the patients with 90-day recurrent stroke in the intensive dose group, there was 0 case (0/159) with intermediate metabolism and 4 cases (4/77,5.2%) with poor metabolism, with statistically significant differences ( P=0.011), whereas there were no statistically significant differences in the conventional treatment group and the ticagrelor group ( P>0.05). Conclusions:Screening carriers of CYP2C19 loss-of-function alleles by point-of-care testing can quickly and precisely guide the treatment of patients with non-cardiogenic HR-NICE. An intensive clopidogrel dose of 150 mg, once a day combined with aspirin was effective in reducing stroke recurrence with less occurrence of any bleeding and adverse events, and patients with intermediate CYP2C19 metabolism may be the best population to benefit.

【Objective:】 To understand the true experience and feelings of nurses in the intensive care unit on the clinical experience of moral dilemmas, and to provide strategies for reducing the impact of moral dilemmas. 【Methods:】 Thirteen nurses in the intensive care unit were interviewed face to face by descriptive nature research method. The traditional content analysis method were used to compute the data, and the coding, categorization and topic extraction were carried out cyclically until the data were saturated and the interview was stopped. 【Results:】 The moral dilemma experience of nurses in the intensive care unit had the following three themes: negative psychological experience, negative behavior experience, and life and death cognitive experience. 【Conclusion:】 Nurses in the intensive care unit will have complex negative experiences after experiencing moral dilemmas. This negative experience threatens nurses’ mental health. Nursing managers should pay attention to the impact of moral dilemmas on nurses and formulate effective measures, thereby ensure nursing safety and maintain the healthy development of the nursing team.

Objective:To understand the present situation of occupational benefit and job satisfaction of nurses in Guangzhou medical and nursing institutions, and to analyze the influencing factors of occupational benefit, so as to provide reference for the managers of pension institutions to formulate measures.Methods:A total of 83 in-service nurses from four medical and nursing institutions in Guangzhou were selected by convenient sampling. The general data questionnaire, nurses′ occupational benefit scale, job satisfaction scale, organizational support scale and job input scale were used to adjust the questionnaire.Results:The total score of occupational benefit of nurses in Guangzhou medical and nursing institutions was 106.14±16.38, which was in the middle level. Among them, the score of good nurse-patient relationship (76.40%) was the highest, the score of positive occupational perception(69.20%) was the lowest, and the total score of job satisfaction was 95.25±14.06. Among them, the score of satisfaction with colleagues (76.87%) was the highest, and the score of welfare treatment and professional development opportunity (55.40%, 56.15%) was lower. The total scores of organizational support and work input were 40.18 ± 9.58 and 54.92 ± 9.58, respectively. The results of multiple linear regression showed that nurses′ age, job satisfaction, organizational support and job input were the important factors affecting nurses′ sense of professional benefit( t values were -3.518-6.668, P<0.01 or 0.05). Conclusions:The managers of pension institutions should take positive measures to improve the welfare treatment of nurses, increase their professional development opportunities, strengthen emotional support for nurses, improve nurses′ concentration and energy input to work, so as to improve nurses′ sense of professional benefit and job satisfaction.

Objective To enhance the recognition of the ethical principles and provide reference for the ethical review in medical research involving human subjects.Methods By summarizing the ethical review of the projects involving human subjects in past three years,analyzing common issues identified,and proposing the corresponding solutions.Results Conducting ethical review for research involving human subject according to ethical principles,is helpful for the protection of human subject,and also for the internationalization of medical research in China.Conclusions For the development of medical research in long term,the ethical review is necessary.All investigators need to improve their understandings and execute the ethical principles well in their research practice.

OBJECTIVE:To prepare Resveratrol-poloxamer 188-solid dispersion(RES-P188-SD)and study its dissolving char-acteristic in vitro and antibacterial activity. METHODS:With P188 as the carrier, solvent method was used to prepare RES-P188-SD. With the mass ratio of drug to carrier,melting temperature and mesh number as the observed factors,and solubility and yield of RES as the observed indexes,L9(34)orthogonal test was designed to optimize the preparation technology,and compre-hensive score of observed indexes were analyzed. The verification test was carried out. After RES-P188-SD was prepared by the op-timal technology,basket method was used to determine its dissolution rate and then its accumulative dissolution rate was calculat-ed,scanning electron microscopy to analyze phase characterization and cylinder-plate method to determine antibacterial activity. RE-SULTS:The optimal technology was as follows as the mass ratio of drug to carrier of 1∶10,melting temperature of 70 ℃ and mesh number of 80. For the sample prepared by the optimal technology,average solubility was 0.51 mg/ml (RSD=1.96%,n=3),average yield was 91%(RSD=0.64%,n=3),average 15 min accumulative dissolution rate was up to 83%(RSD=0.69%, n=3);the drug in amorphous form was homogenously distributed in the carrier;RES-P188-SD could inhibit Staphylococcus aure-us and Escherichia coli. CONCLUSIONS:The optimal technology is stable and feasible,by which RES-P188-SD has been pre-pared successfully,providing reference for increasing the solubility,dissolution rate and antibacterial activity of RES.

Objective To evaluate the emotions and quality of life in the patients with thyroid-associated ophthalmopathy (TAO) .Methods 38 TAO patients with normal thyroid function and 34 healthy subjects were recruited .The patients with TAO were further divided into the mild and moderate-severe group by EUGOGO criteria .The depressive and anxious status and quality of life of all subjects were assessed by the rating scales .Results The incidence rate of anxiety and depression in the patients with TAO was 36 .8% and 28 .9% separately ,which were higher than 8 .8% and 5 .9% in the controls(P<0 .05) ,but the quality of life scores in TAO patients were lower than those in the controls (P<0 .05) .The subgroup analysis indicated that the incidence rate of anxiety and depression in female TAO patients was 50 .0% and 45 .5% separately ,which were higher than that in male TAO pa-tients 18 .8% vs .6 .3% (P<0 .05) ,but the quality of life scores in female TAO patients were lower than those in male TAO pa-tients(P<0 .05) .Compared with the mild-moderate group ,an obviously higher incidence rate of anxiety (21 .7% vs .60 .0% ,P<0 .05) and depression(8 .7% vs .60 .0% ,P< 0 .05) were observed in the severe group with the lower quality of life scores (P<0 .05) .Conclusion (1) TAO affects the emotions and the quality of life of TAO patients .(2) TAO patients have a statistically higher incidence rate of anxiety and depression and a lower quality of life ;this phenomenon is more obvious in female patients .(3) The patients with severe TAO are more likely to have anxiety and depression ,as well as a lower quality of life .

Objective To study the basic pathogenic cause,clinical characteristics,treatment methods and prognosis of sub-acute infective endocarditis (IE) ,and to improve the diagnosis and treatment against it Methods The basic cardiac disease,clinical characteristics,pathogenic bacteria,ultrasound cardiogram, therapy and prognosis of 36 cases of sub-acute IE was retrospectively analyzed. Results Compared to previous reports, the proportion of rheumatic cardiac disease was a little lower, whereas the proportion of congenital cardiac disease and not-recorded cardiac diseases were a little higher.The main clinical characteristics showed as fever, heart failure, increasing in number of neutrophile granulocyte,blood sedimentation and anemia, The positive rate of blood culture was 58. 33% with the most common pathogenic bacterium of streptococcus viridans. Endocardial vegetation has been diagnosed in 63. 89% of patients through-thoracic echo-cardiography. The short-term fatality rate was 19. 44% . Conclusions There have been significant changes in the basic pathogenic causes,clinical characteristics and pathogenic bacteria of sub-acute IE as compared to the previous reports. The fatality rate remains high even after active treatment. Early surgical operation is recommended to those suitable patients.