Analysis on the Psychosomatic Demands of Dying Patients in Hospice Care / 中国医学伦理学

Under the background of aging, the hospice care of the elderly, disability and dementia, and critically ill patients has attracted more and more attention. This paper discussed the ways to improve the quality of life of dying patients and proposed a method of whole-person, whole-family, whole-team care and companionship while doing medical treatment of this group. It also put forward suggestions: take hospice care as a strategic project to deal with aging, incorporate it into the Healthy China strategy, encourage more doctors, volunteers and caring people to join the hospice care team in terms of policy and employment orientation, and promote medical colleges from the aspects of disciplines, courses, teachers and examination, so as to constantly explore a more reasonable and warmer hospice care mechanism and model, alleviate the physical and mental problems of patients and let life end with more dignity.

Advances in the correlation between digital eye strain and sleep quality in adolescents / 中国学校卫生

Abstract@#Digital eye strain can affect not only adolescents visual health, but also sleep quality. In order to provide a reference for safeguarding adolescents visual health and physical health, the paper reviews the direct correlation, feedback correlation, mediating role and the mechanisms between their digital eye strain and sleep quality, as well as proposes some strategies to reduce digital eye strain and improve sleep quality, such as screen time limits, adjusting the brightness and contrast of electronic screen devices, maintaining correct posture and viewing distance, increasing eye nutrition and protection, establishing a regular sleep routine, avoiding the use of electronic screen devices before bedtime, creating a comfortable and quiet sleep environment, and paying attention to the effects of diet and exercise.

Influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation / 器官移植

Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.

Progress of research on tumor organoids: A bibliometric analysis of relevant publications from 2011 to 2021.

Background: Research on tumor organoids has developed rapidly over the past 20 years, but a systematic analysis of current research trends is lacking. Researchers in the field need relevant references and knowledge of current research hot spots. Bibliometric analysis and visualization is a systematic method of acquiring an in-depth understanding of the status of research on tumor organoids. Methods: CiteSpace, VOSviewer and the Bibliometric Online Analysis Platform from the Web of Science Core Collection were used to analyze and predict publishing trends and research hot spots worldwide in the field of tumor organoids. Results: A total of 3,666 publications on tumor organoids were retrieved, and 2,939 eligible articles were included in the final analysis. The number of publications has grown significantly, with the United States of America as the leading country for research on tumor organoids. Among journals, Cancers published the largest number of articles. Harvard Medical School published the highest number of articles among all institutions. The Chinese Academy of Sciences was ranked highest among all contributing institutions on the importance of their publications. A trend in multi-disciplinary collaboration was observed in studies on tumor organoids. Keywords indicated that the current research largely concentrated on optimizing the construction of organoid models to use for medication development and screening in the clinical setting, and to provide patients with individualized treatment for gastric cancer and colorectal cancer, which are newly emerging research hotspots. Gastric and colorectal cancers were the top two tumors that have received increasing attention and have become the focal points of recent studies. Conclusion: This study analyzed 2,939 publications covering the topic of tumor organoids. Although optimizing the construction of organoid models has always been a hot topic in this field, the application of tumor organoids to the development of medications and screenings will foster individualized treatment for patients, which is another emerging hot spot in this field of research.

Research on outpatient capacity planning combining lean thinking and integer linear programming.

BACKGROUND: The size and cost of outpatient capacity directly affect the operational efficiency of a whole hospital. Many scholars have faced the study of outpatient capacity planning from an operations management perspective. OBJECTIVE: The outpatient service is refined, and the quantity allocation problem of each type of outpatient service is modeled as an integer linear programming problem. Thus, doctors' work efficiency can be improved, patients' waiting time can be effectively reduced, and patients can be provided with more satisfactory medical services. METHODS: Outpatient service is divided into examination and diagnosis service according to lean thinking. CPLEX is used to solve the integer linear programming problem of outpatient service allocation, and the maximum working time is minimized by constraint solution. RESULTS: A variety of values are taken for the relevant parameters of the outpatient service, using CPLEX to obtain the minimum and maximum working time corresponding to each situation. Compared with no refinement stratification, the work efficiency of senior doctors has increased by an average of 25%. In comparison, the patient flow of associate senior doctors has increased by an average of 50%. CONCLUSION: In this paper, the method of outpatient capacity planning improves the work efficiency of senior doctors and provides outpatient services for more patients in need; At the same time, it indirectly reduces the waiting time of patients receiving outpatient services from senior doctors. And the patient flow of the associate senior doctors is improved, which helps to improve doctors' technical level and solve the problem of shortage of medical resources.

Research progress on therapeutic DC vaccine against melanoma / 药学实践杂志

Melanoma is the most aggressive skin malignant tumor, which is prone to early metastasis and relapse after treatment. Therapeutic tumor vaccines are new immunotherapies, which have the advantages of low toxicity and inhibiting tumor metastasis. Melanoma has a high mutation load and a large number of specific antigens. Currently, various types of tumor vaccines have been developed for melanoma, especially those based on dendritic cells (DC). Although the efficacy of therapeutic DC vaccines in melanoma has been confirmed by a number of studies, these vaccines still have problems such as insufficient immune effect and poor efficacy when used alone, and there is still a large room for improvement. In this paper, the current research status of therapeutic DC vaccines for melanoma was reviewed, and the research key points and optimization strategy of therapeutic DC tumor were prospected.

The efficacy of different treatment modes for locoregional recurrence after nephrectomy in patients with renal cell carcinoma / 中华泌尿外科杂志

Objective:To investigate the efficacy of different treatment modes for locoregional recurrence after nephrectomy in patients with renal cell carcinoma.Methods:A total of 106 patients with locoregional recurrence after nephrectomy without distant metastasis (77 males and 29 females) admitted to Sun Yat-sen University Cancer Center from October 2001 to July 2020 were retrospectively analyzed. The median age was 51 (40, 60) years old. Radical nephrectomy was performed in 90 patients with primary tumor and partial nephrectomy was performed in 16 patients. Pathological diagnosis showed that 54 cases were clear cell carcinoma and 52 cases were non-clear cell carcinoma. 53 cases were in stage T 1-2 and 53 cases in stage T 3-4. The median diameter of recurrent lesions was 3.2 (2.0, 6.3) cm, and the median number was 2 (1, 4). The recurrence sites were divided into renal fossa recurrence (33 cases), renal fossa±retroperitoneal lymph node recurrence (38 cases), and intra-abdominal spread (35 cases). The median duration from primary surgery to local recurrence was 14.8 (7.3, 35.8) months. Two treatment groups were identified as systemic therapy alone (Group A) and local therapy with or without systemic therapy (Group B). The Kaplan-Meier method was used to compare the progression free survival (PFS) and overall survival (OS) between Group A and Group B. The Cox model was used to perform univariate and multivariate analysis. Results:Of all the 106 patients, 33 patients were in Group A and 73 patients were in Group B. In Group A, 29 patients (87.9%) received targeted therapy, and 4 patients (12.1%) received targeted therapy combined with immunotherapy. In Group B, 34 patients (46.6%) received surgery or ablation and 39 patients (53.4%) received SBRT, of which 62 patients (84.9%) received concurrent systemic therapy. Among them, 58 patients (93.5%) received targeted therapy, and 4 patients (6.5%) received targeted therapy combined with immunotherapy. The median follow-up period was 29.0 (15.4, 45.9) months, 64 patients progressed on tumor including 28 patients died. The median PFS and OS were 15.6 (7.1, 35.2) months and 66.9 (37.8, not reached) months. The median PFS of Group A and Group B were 7.6(5.0, 17.2)months and 22.2(9.6, 63.9)months respectively ( P=0.001), median OS of Group A and Group B were 45.7 (23.4, 62.8)months and 71.0(50.6, not reached)months respectively, and the 2-year OS were 70.6% and 85.5% in Group A and Group B respectively ( P=0.023). The univariate analysis showed local therapy with or without systemic therapy was significantly reduced 56% risk of tumor progression ( HR=0.44, P=0.003) and reduced 60% risk of death ( HR=0.40, P=0.028). The multivariate analysis showed that the OS was associated with ECOG score( HR=10.20, 95% CI 4.13-25.30, P<0.001)and local therapy( HR=0.23, 95% CI 0.09-0.58, P=0.002). Conclusion:Compared with systemic therapy alone, local therapy with or without systemic therapy can effectively improve the PFS and OS of patients with locoregional recurrence after nephrectomy.

Correlation between self-efficacy and discharge readiness in patients with enterostomy / 中华健康管理学杂志

Objective:To explore the correlation between self-efficacy and discharge readiness in patients with enterostomy.Methods:It was a cross-sectional study. Using the self-efficacy Scale and the Readiness for Discharge Scale as research tools, the patients who underwent enterostomy in the Department of General Surgery of Peking Union Medical College Hospital from December 2018 to December 2019 were conveniently selected for questionnaire survey. Statistical descriptive variables such as mean values, median values and frequency were used to investigate the current situation of self-efficacy and discharge readiness of patients with enterostomy. Pearson correlation analysis (or Spearman correlation analysis) was used to explore the correlation between self-efficacy and discharge readiness in these patients.Results:The total self-efficacy score of the 121 patients with enterostomy was (75.81±21.16) points, and the total discharge readiness score was (138.11±34.60) points. The total score of self-efficacy in the patients with enterostomy was positively correlated with the total score of readiness for hospital discharge ( r=0.379, P<0.01). No correlation was found between the self-condition dimension and the confidence and efficacy of sexual life ( r=0.125, P>0.05) and the confidence and efficacy of sexual life satisfaction ( r=0.062, P>0.05). The disease knowledge dimension was positively correlated with the following variables, self-efficacy score ( r=0.311, P<0.01), stoma care efficacy ( r=0.358, P<0.01), self-social efficacy ( r=0.227, P<0.05), diet choice efficacy ( r=0.221, P<0.05) and stoma self-care confidence efficacy ( r=0.249, P<0.01). The post-discharge coping ability dimension was positively correlated with the total score of self-efficacy ( r=0.428, P<0.01). Anticipatory social support dimension was positively correlated with self-efficacy ( r=0.218, P<0.05), self-social efficacy ( r=0.226, P<0.01), vitality confidence ( r=0.202, P<0.05) and stoma self-care confidence ( r=0.198, P<0.05). Conclusion:The self-efficacy level of patients with enterostomy can positively predict the level of readiness for discharge.

Prevalence trend and related factors of scoliosis and myopia co-morbidities among primary and middle school students in Inner Mongolia Autonomous Region from 2019 to 2022 / 中国学校卫生

Objective@#To analyze the prevalence trend of scoliosis among myopic students in Inner Mongolia Autonomous Region during 2019-2022, to explore the common etiology of myopia and scoliosis co-morbidities, so as to provide a reference for the development of relevant measures.@*Methods@#The method of stratified random cluster sampling was used to select 181 533, 141 552 , 200 987, 190 918 primary and secondary school students from 12 leagues(103 banners) in Inner Mongolia Atuonomous Region in September each year from 2019 to 2022. And scoliosis screening, vision examination and questionnaire survey were conducted among students in the included studies. The χ 2 test was used to analyze the data, and the binary multivariate Logistic regression model was used to screen the influencing factors of scoliosis and myopia co-morbidities.@*Results@#From 2019 to 2022, the myopia rate of primary and secondary school students in Inner Mongolia Autonomous Region was 55.55%-59.72%, scoliosis rate was 1.56 %-2.81% and the rates of scoliosis and myopia co-morbidities were 1.14%-1.95%, and the difference between different years was statistically significant ( χ 2=595.01, 775.56, 461.84, P < 0.05 ). In 2022, the co-morbidity rate was higher in girls than in boys(1.32% vs 0.97%), the rate of urban areas was higher than that of rural areas(2.57% vs 0.62%), the rate of students in vocational high school and high school was higher than that in junior high school and primary school (3.82%,2.47% vs 1.70%,0.42%), the rate of over developed areas was higher than that of poor areas (1.21% vs 0.99%)( χ 2=52.19, 1 269.82, 1 361.52, 17.29, P < 0.05 ). Logistic regression analysis showed that at least 1 h of moderate and high intensity exercise every day on weekends, the number of physical education classes per week was more than 3 sessions, the height of desks and chairs was adjusted according to height, resting outdoors, limiting screen time, and strictly requiring standing and sitting posture were the negative correlated with scoliosis and myopia, and the OR value was 0.65-0.90, reading books or electronic screens while participating in cram classes, walking or riding in the car were positively correlated with comorbid scoliosis and myopia, and the OR values were 1.27 and 1.13 ( P < 0.05), respectively.@*Conclusion@#Behavioral habits severely affect scoliosis and myopic of students. Prevention and control of scoliosis and myopia co-morbidity should start with students behavioral habits, early screening and early intervention.

Pharmacodynamic mechanism study on Modified sanhuang ointment in the treatment of anal ulcers and swelling in rats / 中国药房

OBJECTIVE To explore the improvement mechanism of Modified sanhuang ointment on anal ulcers and swelling model rats. METHODS The anal ulcer model of the rat was induced by using glacial acetic acid； the effects of Modified sanhuang ointment low-dose， medium-dose and high-dose groups （185， 370， 740 mg/kg）， western medicine positive control group （Compound carraghenates cream， 1 g/kg） and TCM positive control group （Mayinglong shexiang zhichuang ointments， 1 g/kg） on body weight， area of anal ulcer， grade of anal ulcer were investigated. The other groups of rats were used to induce rectal swelling models with croton oil； the effects of Modified sanhuang ointment low-dose， medium-dose and high-dose groups （185， 370， 740 mg/kg）， western medicine positive control group （Compound carraghenates cream， 1 g/kg） and TCM positive control group （Mayinglong shexiang zhichuang ointments， 1 g/kg） on the rate of rectal and anal swelling， serum contents of inflammatory factors [interleukin 2 （IL-2）， IL-4， tumor necrosis factor （TNF-α）]， pathological morphology of rectal tissue， the expression of transient receptor potential channel V1 （TRPV1） and substance P in rectal tissue and rectal vascular permeability were investigated. RESULTS In Modified sanhuang ointment， the increase in body weight was enhanced， and the area of anal ulcers， as well as the grade of anal ulcers in rats with anal ulcer models， were reduced to varying degrees； rectal tissue damage in rectal swelling model rats was improved； the rate of rectal and anal swelling， the serum contents of inflammatory factors， the expressions of TRPV1 and substance P in rectal tissue， and rectal vascular permeability were all decreased （P＜0.05 or P＜0.01）. The effect of Modified sanhuang ointment was better than that of western medicine positive control and TCM positive control.Modified sanhuang ointment can improve anal ulcers and swelling in rats by reducing the release of inflammatory factors， inhibiting the expression of TRPV1 and substance P.

Analysis of 8 Cases of Blau Syndrome/Early-onset Sarcoidosis——Clinical Manifestations, Histopathology Features and Gene Mutation Diversity / 罕见病研究

  Objective  To summarize the clinical manifestations, pathological features and gene mutation diversity of Blau syndrome/early-onset sarcoidosis.  Methods  We collected general data, clinical manifestations, and auxiliary examination results from 8 patients who were diagnosed of Blau syndrome/early-onset sarcoidosis and treated in our hospital from January 2011 to December 2022, and then summarized and analyzed their characteristics and diversity.  Results  Among the 8 patients, 4 were males and 4 were females. The onset age was 3 to 8 months old. Rash was the first symptom in 7 patients(87.5%). 6 patients(75.0%) had papules and erythema.3 cases(37.5%) had arthritis. 2 cases(25.0%) had uveitis and other eye inflammation. 4 cases (50.0%) also showed intermittent fever. 3 cases (37.5%) showed symptoms in nerve and respiratory system, and hypertension respectively. The skin histopathology of 8 patients showed non-caseous granuloma formation. In laboratory detection, CRP and TNF-α were significantly increased before treatment, while IL-6, IL-8, TNF-α and IL-2 receptor(IL-2R) were significantly decreased in 5 patients after glucocorticoid therapy. The results of genetic testing showed that 4 of the 7 patients had p.R334W(c.1000C > T) mutation, 1 had p.H313R(c.938A > G) and p.R471C(c.1411C > T)double mutation, and 1 had p.476_477del (c.1427_1429delcct).  Conclusions  Blau syndrome/early-onset sarcoidosis has significant features in clinical manifestations, histopathology and gene mutation, but it also has diversity.

Correlation analysis of glucose and lipid metabolism in elderly patients with Helicobacter pylori infection complicated with metabolic syndrome / 公共卫生与预防医学

Objective To investigate the correlation of glucose and blood lipid metabolism in elderly patients with Helicobacter pylori (Hp) infection complicated with metabolic syndrome (MS), and to provide theoretical basis for clinical diagnosis and treatment of MS patients. Methods A total of 176 elderly MS patients treated in our hospital from February 2020 to February 2021 were selected. Uremic [13C] tablet breath test kit was used to determine Hp infection. According to Hp infection, they were divided into Hp positive group (n=59) and Hp negative group (n=117). Glucose metabolism indexes (FBG, 2hPG, HbA1c, FINS) and serum lipid metabolism indexes (TC, HDL-C, LDL-C) were determined in all subjects. Risk factors of Hp infection in MS patients were analyzed by multivariate logistic regression. Pearson correlation analysis was conducted between sreum LDL-C, HbA1c and FINS levels and DOB value in MS patients. Results The levels of FBG, 2hPG, HbA1c, FINS and LDL-C in Hp positive group were significantly higher than those in Hp negative group (P0.05). It showed that LDL-C, HbA1c and FINS were independent risk factors for Hp infection in MS patients (P<0.05). Pearson correlation analysis showed that There was a positive correlation between DOB and LDL-C, HbA1c and FINS levels in MS patients (r=0.475,0.512,0.459,P<0.05). Conclusion Hp infection can affect glucose and lipid metabolism in elderly MS patients, and there is a close relationship between Hp infection and ldL-C, HbA1c and FINS levels in elderly MS patients.

Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells

Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8+ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.

Rapid Identification of Characteristic Chemical Constituents of Panax ginseng, Panax quinquefolius, and Panax japonicus Using UPLC-Q-TOF/MS.

Saponins are the main active components in Panax ginseng C. A. Mey. (PG), Panax quinquefolius L. (PQ), and Panax japonicus C. A. Mey. (PJ), which belong to the genus Panax in the Araliaceae family. Because the chemical components in the three species are similar, they are often mixed and misused in functional foods and pharmaceuticals applications. Therefore, it is urgent to establish a method to quickly distinguish among PG, PQ, and PJ. Ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was combined with data postprocessing to identify the main characteristic fragments (CFs) and the related neutral losses (NLs) of protopanaxadiol (PPD), protopanaxatriol (PPT), oleanolic acid (OLE), and ocotillol- (OCO-) type saponins. By comparing the mass spectral data, it was possible to rapidly classify and identify saponins in PG, PQ, and PJ. A total of twenty-three chemical components were identified in the PG samples, twenty-three components were identified in the PQ samples, and twenty-seven components were identified in the PJ samples. Among them, OCO-type saponins were characteristic of PQ and PJ. Ginsenoside Rf, which was absent from PQ, allowed for differentiation between PQ and PJ. The CFs and NLs in the mass spectra of the characteristic components of PG, PQ, and PJ allowed for the rapid classification and identification of these species. Additionally, these results provide technical support for the quality evaluation of Chinese herbal medicine and for constructing a scientific regulatory system.

Healthy City construction survey among residents living in Hangzhou City / 预防医学

Objective@#To investigate the awareness of and participation in Healthy City construction among residents in Hangzhou City, so as to provide insights into promotion of participation in Healthy City construction.@*Methods@#Residents at ages of 15 to 75 years were sampled using the multi-stage stratified random sampling method, from 30 townships in Jianggan, Xiaoshan and Tonglu counties of Hangzhou City from November 2019 to July 2020, and a questionnaire survey of 10 representative projects pertaining to Healthy City construction in Hangzhou City was performed to investigate the awareness of and participation in Healthy City construction.@*Results@#A total of 5 559 questionnaires were allocated, and 5 211 valid questionnaires were recovered, with an effective recovery rate of 93.74%. The respondents had a mean age of ( 43.82±17.25 ) years, and included 2 280 males ( 43.75% ) and 2 931 females ( 56.25% ). The overall standardized awareness and participation rates of Healthy City construction were 81.73% and 48.58% among the respondents. The projects with the three highest awareness included healthy environment improvements ( 92.67% ), travelling by public transportation ( 92.22% ) and tobacco control action ( 91.04% ), while the projects with the three lowest awareness included chronic disease management ( 75.57% ), maternal and child healthcare ( 72.73% ) and “Healthy Cell” Program ( 45.56% ). The projects with the three highest participation rates included travelling by public transportation ( 74.59% ), healthy environment improvements ( 65.17% ), tobacco control action ( 61.52% ), while the projects with the three lowest participation rate included chronic disease management ( 35.92% ), “Healthy Cell” Program ( 34.96% ) and maternal and child healthcare ( 33.20% ).@*Conclusions@# The overall proportion of participation in Healthy City construction is low among residents in Hangzhou City, and notably, the awareness rate of and the proportion of participation in chronic disease management, maternal and child healthcare and “Healthy cell” Program are both low.

Risk factors for herb-induced liver injury / 临床肝胆病杂志

Drug-induced liver injury (DILI) is one of the common adverse drug reactions and is the main cause of withdrawal of drugs after marketing, which has attracted more and more attention of the public, and herb-induced liver injury (HILI) is a special type of DILI. In recent years, the frequent occurrence of HILI not only seriously endangers the health of patients, but also causes the controversy over the safety of traditional Chinese medicine. Therefore, this article reviews the potential risk factors for HILI from the three aspects of "patient", "drug", and "use", so as to provide a basis for the objective identification, prevention, and control of HILI and a reference for the construction of traditional Chinese medicine pharmacovigilance system represented by liver injury.

Mechanism of action of nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome in liver diseases / 临床肝胆病杂志

Inflammasomes play an important role in the innate immunity of the liver; however, the excessive activation of inflammasomes can lead to liver inflammation and injury. The mechanism of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-mediated liver injury has been extensively studied. Related studies have shown that the development of various liver diseases may be associated with the excessive activation of inflammasomes, especially NLRP3 inflammasome. This article reviews inflammasomes, the activation mechanism of NLRP3 inflammasome, and the role of NLRP3 inflammasome in different liver diseases, so as to provide a reference for the treatment targets of liver diseases from the perspective of NLRP3 inflammasome.

Effects of endothelial progenitor cell-derived exosomes on neuronal injury induced by oxygen-glucose deprivation and restoration / 中华麻醉学杂志

Objective:To evaluate the effects of endothelial progenitor cell (EPC)-derived exosomes on neuronal injury induced by oxygen-glucose deprivation and restoration (OGD/R).Methods:HT22 neurons of mice were cultured and divided into 3 groups ( n=30 each) using a random number table method: control group (C group), OGD/R group and OGD/R plus EPC-derived exosome group (OGD/R+ EXO group). Cells in group C were cultured in normal atmosphere.In group OGD/R, the cells were exposed to 94%N 2-1%O 2-5%CO 2 for 6 h in glucose- and serum-free DMEM medium, followed by 24 h restoration of O 2 and glucose in the normal medium.In group OGD/R+ EXO, 20 μg/ml EPC-derived exosomes were added to the culture medium at 24 h before developing the model.EPCs were identified by immunofluorescence staining.Exosomes were identified by Western blot, transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Cell viability was measured by CCK-8 assay, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by enzyme-linked immunosorbent assay.The neuronal apoptosis was detected by TUNEL staining, and the apoptosis rate was calculated.The expression of Bax, Bcl-2, caspase-3, and cleaved caspase-3 was determined by Western blot, and cleaved caspase-3/caspase-3 ratio was calculated. Results:The cultured cells were EPCs, and EPC-derived exosomes were successfully extracted.Compared with group C, the cell viability was significantly decreased, the content of MDA was increased, the activity of SOD was decreased, the apoptosis rate was increased, the expression of Bax was up-regulated, the expression of Bcl-2 was down-regulated, and the ratio of cleaved-caspase-3/caspase-3 was increased in group OGD/R and group OGD/R+ EXO ( P<0.05). Compared with group OGD/R, the cell viability was significantly increased, the content of MDA was decreased, the activity of SOD was increased, the apoptosis rate was decreased, the expression of Bax was down-regulated, the expression of Bcl-2 was up-regulated, and the ratio of cleaved-caspase-3/caspase-3 was decreased in group OGD/R+ EXO ( P<0.05). Conclusions:EPC-derived exosomes can reduce OGD/R-induced neuronal injury, which is related to inhibition of oxidative stress and neuronal apoptosis.

Construction and in vitro evaluation of AIE self-assembled probe based on GSH response covalent cyclization / 国际生物医学工程杂志

Objective:To construct an aggregation induced emission (AIE) self-assembled probe based on glutathione (GSH) response covalent cyclization and evaluate it in vitro.Methods:The peptide sequence containing the 2-cyano-6-aminobenzothiazole-cysteine (CBT-Cys) condensation sequence was synthesized by the solid-phase peptide synthesis method. After coupling with an AIE molecule by click chemical reaction, an AIE self-assembled probe 1 based on GSH response covalent cyclization was constructed, and probe 2 lacking Cys structure was used as the control. The absorption and emission spectra of probes were tested and the specificity of probes to GSH was analyzed. The hydrodynamic diameter and structure of the probes after response were compared. The effects of different pH values, temperatures, probe concentrations, and GSH concentrations on fluorescence intensity were investigated. The toxicity of probes to tumor cells such as HeLa, HepG2 and MDA-MB-231 was evaluated.Results:After GSH response, the fluorescence of probe 1 was enhanced by about 6 times and that of probe 2 was enhanced by about 2 times; probe 1 was converted into a dimer with a hydrodynamic diameter of about 896.1 nm. Probe 2 lacked a cyclization motif and was converted into a monomer with a hydrodynamic diameter of about 427.4 nm. The fluorescence intensity of probe 1 was significantly higher than that of probe 2 at pH=7.0 and 37 ℃, and the toxicity of probes to tumor cells (HeLa, HepG2 and MDA-MB-231) was low.Conclusions:After the disulfide bond of probe 1 was reduced by GSH, the probe molecule lost the hydrophilic sequence, resulting in fluorescence turn-on (the first aggregation), and probe 1 immediately generates an AIE dimer (the second aggregation) because it contains a CBT-Cys cyclization sequence, which realizes the dual AIE effect compared with the single aggregation of probe 2, and significantly enhances the fluorescence emission. Probe 1 has better applicability in physiological environments, which provides an idea for in-situ generation of covalent cycling probes in vivo and is expected to be used in tumor imaging and treatment in the later stages.

The mechanism of chelerythrine against breast cancer by network pharmacology and molecular docking / 西安交通大学学报(医学版)

【Objective】 To investigate the mechanisms of chelerythrine on the treatment of breast cancer based on network pharmacology and molecular docking. 【Methods】 The targets corresponding to chelerythrine and breast cancer were obtained from Mala Cards and Swiss Target Prediction databases. Chelerythrine-related and breast cancer-related targets were found and then combined to get an intersection, which represented potential anti-breast cancer targets of chelerythrine. A protein-protein interaction (PPI) network was constructed from the STRING database and key genes were screened using the topological analysis. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of targets were conducted using metascape database. The relationship between the expressions of key target genes and the survival curve was analyzed using the Kaplan-Meier Plotter database. Molecular docking analysis was performed by AutoDock Vina to verify whether chelerythrine has a definite affinity with key targets. 【Results】 A total of 37 potential targets were obtained in chelerythrine against breast cancer. The result of the topology analysis included 8 key targets. The GO enrichment analysis included 317 GO items. The KEGG pathway analysis included 80 pathways, which were closely related to the PI3K/AKT signaling pathway, the ErbB signaling pathway, VEGF signaling pathway, and others. The results of the survival curve analysis showed that the expression levels of CHEK1, PIK3CA, mTOR and PTGS2 genes were related to the survival time of breast cancer patients. The results of molecular docking proved that the combined activity of chelerythrine with key targets was excellent. 【Conclusion】 Chelerythrine may play an anti-breast cancer role via the PI3K/AKT signaling pathway and has the potential to be developed into a clinical drug for breast cancer.